Program Members

Co-Leaders

Ronald Buckanovich

Ronald Buckanovich

Program: Cancer Biology

412-641-4721 buckanovichrj@mwri.magee.edu 204 Craft Avenue, B333
Pittsburgh PA
Summary

Ovarian cancer is a disease that has high rates of resistance to both chemotherapy and immunotherapy. This therapeutic resistance drives a poor prognosis for patients with ovarian cancer. A primary focus of my group is to understand therapeutic resistance and develop therapeutic approaches to overcome this resistance. We are working to understand both cancer cell inherent mechanisms of therapeutic resistance and how interactions with host cells in the tumor microenvironment increase therapeutic resistance. 

We are currently focusing on understanding the biology of a population of slowly dividing/non-dividing or ‘quiescent’ cancer cells. These quiescent cells are inherently resistant to chemotherapy and radiation therapy – both of which kill fast growing cells. Upon exposure to chemotherapy, we find that these cells quiescent cells secrete novel factors to make neighboring cells resistant to both chemotherapy and immunotherapies. Following completion of chemotherapy treatment these quiescent cells can resume proliferation and drive disease recurrence. 

Furthermore, following chemotherapy exposure, these cells secrete additional factors which create an immunosuppressive microenvironment. Given the critical role of these cells in therapeutic resistance, we are developing novel therapeutic approaches to kill these otherwise resistant cells. Based on our findings we are currently running two different clinical trials to determine if we can prevent chemotherapy or immunotherapy resistance.  

Research Interests and Keywords
  • cancer stem cells,ovarian cancer,targeted therapies,tumor vasculature
Read More about Ronald Buckanovich
Steffi Oesterreich

Steffi Oesterreich

Program: Cancer Biology

oesterreichs@upmc.edu The Assembly
5051 Centre Ave
Pittsburgh PA
Summary

The main interest of Dr. Oesterreich's laboratory is to further our understanding of hormone action in women's cancers (including both breast and ovarian cancers), with the ultimate goal to use this knowledge for improved diagnosis and endocrine treatment. These studies include many aspects of translational breast cancer research utilizing basic biochemistry, molecular and cell biology, and cell lines, mouse models and clinical samples. Over the last few years, Dr. Oesterreich has developed a strong research interest in in situ and invasive lobular disease, the second most common yet understudied histological subtype of breast cancer. In her role as Director of Education at the Women's Cancer Research Center, Dr. Oesterreich is also very interested in providing outstanding training opportunities to the next generation of women's cancer researchers.

Research Interests and Keywords
  • bone metastases,Breast Cancer,Chromatin,coregulators,Epigenetics,estrogen receptor,invasive lobular carcinoma,lobular carcinoma in situ,mutations,ovarian cancer
Read More about Steffi Oesterreich

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Members

Sameer Agnihotri

Sameer Agnihotri

Program: Cancer Biology

(412) 218-8456 sameer.agnihotri@pitt.edu Rangos Research Center, Room 7126
4401 Penn Avenue
Pittsburgh PA
Summary

The lab has a focus on several topics:
1) It is now appreciated that HGG glioma comprises of several molecular subgroups and that the genetics of pediatric and adult HGG are distinct. Therefore a “one size that fits all” approach to therapy will not be successful. The Agnihotri Laboratory interests include using next-generation sequencing technology to identify and validate driver alterations of various HGG with a focus on DIPG and non-histone mutated “RTK” Glioblastoma (GBM). 
2) A defining hallmark of glioblastoma and DIPG is altered tumor metabolism. The metabolic shift towards aerobic glycolysis with reprogramming of mitochondrial oxidative phosphorylation, regardless of oxygen availability, is a phenomenon known as the Warburg effect. In addition to the Warburg effect, glioblastoma tumor cells also utilize the tricarboxylic acid cycle/oxidative phosphorylation in a different capacity than normal tissue. The Agnihotri Laboratory investigates the metabolic dependencies of brain tumors and if they can provide therapeutic vulnerabilities.
3) The lab uses the genomic and metabolic information to build better representative brain tumor pre-clinical models for testing of novel therapies. Working closely with a clinical team use of these accurate models are essential to start early phase clinical trials.

Read More about Sameer Agnihotri
Katherine Aird

Katherine Aird

Program: Cancer Biology

katherine.aird@pitt.edu The Assembly
5051 Centre Ave
Pittsburgh PA
Summary

The Aird lab focuses on the reciprocal regulation between cellular metabolism and the cell cycle. The interplay between cell cycle and metabolism is bidirectional, although incompletely understood. While proliferating cells require energy and biomass, metabolites can also act as signaling molecules to impact epigenetic and transcriptional programs, thereby influencing biology beyond macromolecule needs. Our lab has made fundamental discoveries into how metabolism informs proliferative cell fate decisions by studying two extremes of proliferation: cancer and cellular senescence. Both cancer and senescent cells are highly metabolically active, yet the outcomes of this rewiring are distinct. We aim to ask fundamental questions related to how the cell cycle informs metabolic decisions and vice versa. Using cancer as a model system, we aim to answer fundamental questions on the bidirectional control of metabolism and the cell cycle.

Our specific questions:

1)    How do metabolic cues lead to differential cell cycle decisions? 

2)    How does cell cycle derangement affect metabolism and what are the consequences of this on intrinsic and extrinsic signaling?

3)    What are the consequences of bidirectional cell cycle and metabolism programs on intrinsic and extrinsic signaling? 

Read More about Katherine Aird
Kelly Bailey

Kelly Bailey

Program: Cancer Biology

412-692-6644 kelly.bailey@chp.edu Pediatric Hematology/ Oncology - 9th Floor
4401 Penn Avenue
Pittsburgh PA
Summary

Dr. Bailey studies pediatric sarcoma biology. Specifically, Dr. Bailey's lab focuses on understanding the intersection of DNA damage and immunobiology in Ewing sarcoma. She is involved nationally in the Children's Oncology Group Bone Tumor Committee and is national Vice Chair of the COG clinical trial AOST2121.

Read More about Kelly Bailey
Riyue Bao

Riyue Bao

Program: Cancer Biology

412-623-0021 baor@upmc.edu UPMC Cancer Pavilion, 1A
5150 Centre Ave.
Pittsburgh PA
Summary

Using a combination of multi-omics data integration, machine learning, and computer vision-assisted pathology image recognition, Dr. Bao’s work bridges methodological advances and biomedical applications with a direct impact on accelerating the knowledge discovery to new clinical trials that could benefit patients. Her lab focuses on the data-driven discovery of resistance mechanisms to cancer immunotherapy, with major contributions to the identification of WNT/ß-catenin activation as the first tumor-intrinsic mechanism that drives immune exclusion, commensal microbiome as the modulator of anti-PD1 efficacy, and systemic discovery of oncogenic pathways that contribute to the absence of immune infiltration across human solid tumors. Those findings are of particular importance because they provide the scientific rationale to new trials that combine therapeutic targets, such as IDH1 inhibitors, with anti-PD1. Dr. Bao is Co-Leader of Bioinformatics/Biostatistics in the Melanoma and Skin Cancer SPORE and Head and Neck Cancer SPORE programs. She also serves as the UPMC Hillman Cancer Center Informatics Committee, providing critical advice on data accessibility, analysis, integration, and infrastructure for translational research across the Cancer Center. Dr. Bao is a member of The American Association of Immunologists, Society for Immunotherapy of Cancer, and Medical Image Computing and Computer Assisted Intervention.

Read More about Riyue Bao
Michael Becich

Michael Becich

Program: Cancer Biology

becich@pitt.edu 5607 Baum Boulevard
Room 521
Pittsburgh PA
Research Interests and Keywords
  • content-based image retrieval and digital libraries
  • oncology informatics
  • prostate tumor cell biology
  • research resource development
  • tissue banking and pathology informatics
  • Translational Bioinformatics
Read More about Michael Becich
Kambez Benam

Kambez Benam

Program: Cancer Biology

(412) 383-4766 kambez.benam@pitt.edu 200 Lothrop St
Rm E1144
Pittsburgh PA
Summary

My lab is focused on development of human Organs-on-Chips (microphysiological systems) and bioinspired robotics in the context of lung and immune pathophysiology. I am interested in applying our Organ-on-a-Chip models to emulate cancer pathobiology preclinically and utilize these platforms for target discovery / therapeutic testing. 

Read More about Kambez Benam
Andrea Berman

Andrea Berman

Program: Cancer Biology

412-624-2200 ajb190@pitt.edu A314 Langley Hall
4249 Fifth Avenue
Pittsburgh PA
Summary

My research focuses on understanding how non-coding RNA directs gene regulation. My current research goals are to understand how RNA conformational change within ribonucleoprotein complexes regulates gene transcription and genome replication. To do this, we will utilize complementary biochemical, structural and computational techniques.

Read More about Andrea Berman
David Boone

David Boone

Program: Cancer Biology

(724) 322-6668 booned@upmc.edu 5607 Baum Boulevard
Suite 414
Pittsburgh PA
Summary

My research interest is focused on lncRNAs in breast cancer. I have strong collaborations with other members of the cancer center including Drs. Adrian Lee, Steffi Oesterreich, Partha Roy, and Uma Chandran. However, my primary role in the cancer center will be centered around training and diversity. I am the Director of the NCI (R25) and DDCF funded Hillman Academy that organizes ~70 internships to high school students annually with a special focus on training underrepresented minorities. I am also the vice chair of the education and training committee for the cancer center.

Read More about David Boone
Ronald Buckanovich

Ronald Buckanovich

Program: Cancer Biology

412-641-4721 buckanovichrj@mwri.magee.edu 204 Craft Avenue, B333
Pittsburgh PA
Summary

Ovarian cancer is a disease that has high rates of resistance to both chemotherapy and immunotherapy. This therapeutic resistance drives a poor prognosis for patients with ovarian cancer. A primary focus of my group is to understand therapeutic resistance and develop therapeutic approaches to overcome this resistance. We are working to understand both cancer cell inherent mechanisms of therapeutic resistance and how interactions with host cells in the tumor microenvironment increase therapeutic resistance. 

We are currently focusing on understanding the biology of a population of slowly dividing/non-dividing or ‘quiescent’ cancer cells. These quiescent cells are inherently resistant to chemotherapy and radiation therapy – both of which kill fast growing cells. Upon exposure to chemotherapy, we find that these cells quiescent cells secrete novel factors to make neighboring cells resistant to both chemotherapy and immunotherapies. Following completion of chemotherapy treatment these quiescent cells can resume proliferation and drive disease recurrence. 

Furthermore, following chemotherapy exposure, these cells secrete additional factors which create an immunosuppressive microenvironment. Given the critical role of these cells in therapeutic resistance, we are developing novel therapeutic approaches to kill these otherwise resistant cells. Based on our findings we are currently running two different clinical trials to determine if we can prevent chemotherapy or immunotherapy resistance.  

Research Interests and Keywords
  • cancer stem cells
  • ovarian cancer
  • targeted therapies
  • tumor vasculature
Read More about Ronald Buckanovich
Timothy Burns

Timothy Burns

Program: Cancer Biology

412-623-7877 burnstf@upmc.edu Hillman Cancer Center Suite 2.18
5117 Centre Avenue
Pittsburgh PA
Summary

My research and clinical interests revolve around the development of targeted therapies for KRAS-mutant NSCLC as well as novel strategies to overcome resistance to targeted therapies for EGFR-mutant and MET-altered NSCLC. My four main research themes are 1) novel pre-clinical target validation and drug development (TWIST1 in oncogene driven NSCLC and TKI resistance; targeting metabolism in oncogene driven lung cancer); and 2) elucidating mechanisms of resistance for targeted inhibitors to develop rationale therapeutic combinations that can be tested in the clinic (Hsp90, ERK1/2 inhibitors and 4th generation EGFR TKIs) and 3) development of targeted therapy approaches for the treatment of brain metastases.  The first line of research in my laboratory focuses on the role of the EMT transcription factor TWIST1 in oncogene-driven NSCLC. We have demonstrated the TWIST1 is essential for lung tumorigenesis for KRAS mutant, EGFR mutant and MET mutant/amplified NSCLC and TWIST1 overexpression leads to resistance to EGFR and MET TKIs. We are examining the mechanism(s) through which this occurs and developing therapeutic combinations to overcome this resistance. Importantly, we have developed a novel TWIST1 inhibitor which serves a tool compound for our therapeutic studies and serves as the basis for our current drug screening efforts to develop a clinical TWIST1 inhibitor. The second line of research in my lab focuses on studying the mechanisms of resistance to targeted agents currently in phase 1 and 2 trials to develop rationale therapeutic combinations in the clinic. This is typified by our previous work with Hsp90 inhibitors and ongoing work on ERK inhibitors and a novel 4th generation EGFR TKI.  Finally, my lab is interested in lung cancer brain metastases, and we are exploring whether targeting the HGF-MET-TWIST1 pathway or downstream metabolic pathways can be an effective strategy for preventing or treating lung brain metastases. In additional to these preclinical studies, we are using both radiogenomic and cell free DNA approaches to predict molecular phenotypes of brain metastases to identify patients with brain metastases that can benefit from MET targeted therapy in the clinic.

Research Interests and Keywords
  • acquired resistance
  • brain metastases
  • chemoresistance
  • Hsp90 inhibitors
  • Lung Cancer
  • Mutant KRAS
  • non-small cell lung carcinoma
  • Oncogenes
  • targeted cancer therapies
  • TWIST1
Read More about Timothy Burns
Carlos Camacho

Carlos Camacho

Program: Cancer Biology

412-648-7776 ccamacho@pitt.edu University of Pittsburgh, Room 3077
3501 Fifth Avenue
Pittsburgh PA
Summary

Dr. Camacho’s main research interests focus on modeling the physical interactions responsible for molecular recognition, and in the development of new technologies for structural prediction, their substrates, and supramolecular assemblies. Any progress in these fundamental problems is bound to bring about a better understanding of how proteins work cooperatively in a cell, promoting breakthroughs in every aspect of the biological sciences. Dr. Camacho has multiple patents in cancer and cancer-related targets.

Read More about Carlos Camacho
Uma Chandran

Uma Chandran

Program: Cancer Biology

chandranur@upmc.edu Room 513
5607 Baum Boulevard
Pittsburgh PA
Summary

I direct the Genomics Analysis Core, a Health Science shared resource and co-direct the Cancer Bioinformatics Services (CBS) for UPMC Hillman Cancer Center. The GAC and CBS’s aims are to 1) provide genomics data analysis, 2) support team science projects such as consortia projects with computational infrastructure for analysis, storage and sharing of large genomics datasets, 3) assist with University of Pittsburgh initiatives for genomics education. GAC and CBS are an interdisciplinary collaboration between my team, the Department of Biomedical Informatics faculty with bioinformatics expertise, UPMC Hillman Cancer Center, the Institute for Personalized Medicine, the Pittsburgh Supercomputing Center (PSC) and the University of Pittsburgh’s Center for Research Computing (CRC). My team and I have experience working with all genomic platforms and applications RNA Seq, Whole Exome Seq (WXS) and Whole Genome Seq (WGS), single cell seq and digital spatial profiling (DSP). We support both cancer and non-cancer studies and from cell culture, model organisms and human datasets such as The Cancer Genome Atlas Project (TCGA).

My team contributes to team science projects by providing expertise in data analysis, metadata annotation, FAIR principles of data sharing and high performance computing. Examples of such projects include the Breast Cancer Research Foundation’s multi-institution AURORA metastatic breast cancer project in which CBS and PSC collaborate in hosting the  data coordination center (DCC). My group also plays a key role in the Breast Cancer Research Foundation’s Data Hub for all 250 BCRF sites.

In the area of genomics education, I teach bioinformatics lectures for DBMI’s Intro to Biomedical Informatics course. My team and I also work closely with the CRC’s genomics education initiative funded by a Pitt seed grant. We have taught hands-on workshops in RNA Seq, metagenomics, single cell genomics and next flow (nf-core) pipelines. The courses are archived and are available through the CRC course website.

Research Interests and Keywords
  • Bioinformatics
Read More about Uma Chandran
Lujia Chen

Lujia Chen

Program: Cancer Biology

(412) 736-7952 luc17@pitt.edu Department of Biomedical Informatics
5607 Baum Blvd, Suite 500
Pittsburgh PA
Summary

Dr. Chen’s research concentrates on developing machine learning methods, especially deep learning models (DLMs) (e.g. Deep Neural Networks, Boltzmann Machine, and topic modeling), to study cancer cell signaling systems, disease mechanisms and cancer pharmacogenomics. Dr. Chen uses the concise representations learned from the DLM with the causal inference to guide the identification of molecular signatures/biomarkers and predicts the clinical outcomes including drug sensitivity and patient survival. Based on Dr. Chen’s strong research background in bioinformatics, biomedical informatics, biology and machine learning, she successfully develops comprehensive AI models that precisely represent the state of signaling systems in cancer cells and use such information to improve the tumor-specific precision medicine (precision oncology).

Read More about Lujia Chen
Yu-Chih Chen

Yu-Chih Chen

Program: Cancer Biology

cheny25@upmc.edu 5117 Centre Ave
Pittsburgh PA
Summary

Due to genomic and epigenetic instability of cancer cells, inter-patient and intra-patient heterogeneity in tumors creates formidable challenges in identifying optimal treatments. To address the challenges, I aim to establish comprehensive high-throughput multi-omics single-cell analysis including genome, epigenome, transcriptome, proteome, functional, and morphological methods. With large amounts of data collected from high-throughput single-cell multi-omics analysis, machine learning techniques can predict patient prognosis and suggest treatments for precision medicine. The integrated approach will change how we understand and treat cancer and ultimately improve outcomes for patients.

Research Interests and Keywords
  • Cancer cellular heterogeneity
  • Machine learning
  • Microfluidics
  • Single-cell analysis
Read More about Yu-Chih Chen
Chakra Chennubhotla

Chakra Chennubhotla

Program: Cancer Biology

412-648-7794 chakracs@pitt.edu Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh
3501 Fifth Avenue, Suite 3081, Biomedical Science Tower 3 (BST3)
Pittsburgh PA
Read More about Chakra Chennubhotla
Amanda Clark

Amanda Clark

Program: Cancer Biology

Summary

The Clark lab focuses on determining the molecular and cellular regulators of metastatic dormancy and recurrence within the liver. We utilize a novel all-human ex vivo 3D liver microphysiological system to model metastasis. The system has not only enabled the recreation of dormant-emergent metastatic cancer progression as observed in vivo but also the identification of mechanisms, candidate biomarkers, and new therapeutic opportunities to target the various stages of metastasis. Our current research centers on i) investigating how dysregulated gut homeostasis drives emergence from metastatic dormancy in the liver, and ii) examining how the bi-directional crosstalk mediated by extracellular vesicles regulates metastatic breast cancer dormancy in the liver.

Read More about Amanda Clark
Lan Coffman

Lan Coffman

Program: Cancer Biology

412-641-2016 coffmanl@mail.magee.edu The Assembly
5051 Centre Ave
Pittsburgh PA
Read More about Lan Coffman
Gregory Cooper

Gregory Cooper

Program: Cancer Biology

Summary

Dr. Cooper is Distinguished Professor, UPMC Endowed Chair, and Vice Chair of Research in the Department of Biomedical Informatics, with a secondary appointment in the Intelligent Systems Program.  His research focuses on the development and application of methods for probabilistic modeling, machine learning, Bayesian statistics, and artificial intelligence to help advance biomedical research and clinical care. He has published over 200 peer-reviewed papers on these and related topics.

His current projects include causal discovery from observational and experimental biomedical and clinical data, personalized cancer outcome prediction, clinical alerting based on machine learning from an electronic medical record (EMR) archive, and infectious disease outbreak detection and characterization. 

Read More about Gregory Cooper
Evan Delgado

Evan Delgado

Program: Cancer Biology

evd7@pitt.edu 200 Lothrop St
South Biomedical Science Tower, Room s433
Pittsburgh PA
Summary

My research interests include:

1. Immune-oncology and immune microenvironment in Hepatocellular Carcinoma
2. Role of scaffold proteins (e.g., IQGAP1) in liver disease and regeneration.
3. Developing a more accurate model of Hepatocellular Carcinoma that efficiently replicates the human disease.

My overall goal is to challenge the unmet need of effective targeted therapies for Hepatocellular Carcinoma (HCC) by studying the immune landscape to develop personalized immunotherapies for HCC. Additionally, it is my goal to develop a model of HCC that better represents the human disease such that novel therapeutic strategies are easily translated into patients. Finally, to tie these goals together, I aim to better understand the molecular mechanisms that contribute to hepatocellular carcinogenesis. For example, I plan to continue studying IQGAP1, a scaffold protein, and its role in hepatocellular biology. Investigating protein-protein interactions regulated by IQGAP1 will expand the current knowledge of HCC and position me as an independent investigator focusing HCC biology and therapeutics.

Read More about Evan Delgado
Vera Donnenberg

Vera Donnenberg

Program: Cancer Biology

donnenbergvs@upmc.edu Division of Hematology/Oncology
Hillman Cancer Center 5117 Centre Avenue
Pittsburgh PA
Summary

Dr. Vera Donnenberg is an Associate Professor of Cardiothoracic Surgery in the School of Medicine at the University of Pittsburgh with a secondary appointment in the Department of Pharmaceutical Sciences in the School of Pharmacy. Dr. Donnenberg’s research focuses on tumorigenic stem cells in lung cancer, esophageal cancer, and breast cancer; pleural metastases; therapeutic resistance; interaction of tumor cells and regenerating tissue; lung immunology; and pleural immuno-oncology. Dr. Donnenberg has written over 395 publications, abstracts, book chapters, and other scientific presentations. Throughout her career she has received numerous awards for her academic and service efforts including the Nathaniel Kwitt Distinguished Service Award from the ACCP, the Marylou Ingram Woman in Science Award from the Coulter Foundation, the Governor’s Distinguished Citizenship Award, Maryland, and the Service Award from the National Society of Black Engineers.

Read More about Vera Donnenberg
Bruce Freeman

Bruce Freeman

Program: Cancer Biology

freerad@pitt.edu E1340 Thomas E. Starzl Biomedical Science Tower
200 Lothrop Street
Pittsburgh PA
Summary

Bruce Freeman, PhD is a biochemist and pharmacologist who investigates eukaryotic cell production and actions of chemically-reactive inflammatory and signal transduction mediators (e.g., superoxide, nitric oxide, peroxynitrite, electrophilic lipids). He is presently the Irwin Fridovich Distinguished Professor and Chair of the Department of Pharmacology and Chemical Biology at the University of Pittsburgh School of Medicin. He, is a founding member of the Vascular Medicine Institute and a member of the University of Pittsburgh Cancer Institute. His laboratory team has made seminal discoveries related to the tissue production and target molecule reactions of reactive inflammatory mediators, which in turn reveals the fundamental process of redox reaction-regulated cell signaling. These insights have led to Dr. Freeman's identification and patenting of new drug strategies for treating metabolic diseases, fibrosis, cancer and acute/chronic inflammatory disorders. His team pioneered the concept that nitric oxide has cell signaling and pathogenic actions modulated by reactions with superoxide  (yielding the oxidizing and nitrating species peroxynitrite) and heme peroxidases (leading to biomolecule oxidation and nitration). His laboratory also discovered that metabolic and inflammatory reactions of unsaturated fatty acids yield electrophilic nitro and keto derivatives, products that manifest potent anti-inflammatory and tissue-protective signaling actions. The discovery of nitric oxide reactions with various oxidases and peroxidases has also revealed clinically-significant mechanisms of catalytic nitric oxide consumption that occur during inflammation and metabolic syndrome. His mass spectrometry-based observations of peroxynitrite, peroxidase and electrophilic fatty acid-induced post-translational protein modifications further underscore the significance of redox reactions in regulating cell and organ function. This work has led to numerous issued patents and ~300 peer-reviewed publications in high impact basic science and clinical journals. The Freeman team’s discoveries of the anti-inflammatory and metabolic actions of electrophilic nitroalkenes also led to the incorporation of Creegh Pharmaceuticals and the now clinical stage evaluation of CP-6 in subjects having obesity-related asthma.  Previously, Dr Freeman was Professor of Anesthesiology, Biochemistry and Molecular Genetics and Environmental Health Sciences at the University of Alabama at Birmingham. He was also Vice Chair for Research in the Department of Anesthesiology and Director of the UAB Center for Free Radical Biology. Prior to service at UAB, he trained at the University of California and Duke University, where he also served on the faculty. He has been the recipient of a number of honors, including being named a Fulbright Research Scholar and serving as an invited lecturer at Nobel Forums. He and his lab team have won more than $40 million in extramural funding to support their research activities. Dr. Freeman's academic leadership has also propelled students, fellows and faculty colleagues into prominent basic science, clinical investigator, legal, patent office and pharmaceutical industry positions.

Research Interests and Keywords
  • Cell Proliferation
  • Drug Discovery
  • free radical
  • Inflammation
  • lipid signaling
  • Nitric Oxide
  • Pharmacology
  • redox signaling
Read More about Bruce Freeman
Ferruccio Galbiati

Ferruccio Galbiati

Program: Cancer Biology

feg5@pitt.edu W1057 Thomas E. Starzl Biomedical Science Tower
Pittsburgh PA
Summary

Most cells can not divide indefinitely due to a process termed cellular senescence. Because cancer cells need to escape cellular senescence in order to proliferate and eventually form tumors, it is well accepted that cellular senescence is a powerful tumor suppressive mechanism. In addition, since several molecular changes that are observed in senescent cells occur in somatic cells during the aging process, investigating the molecular mechanisms underlying cellular senescence will also allow us to better understand the more complicated aging process. Thus, molecules that regulate cellular senescence represent potential therapeutic targets for the prevention and treatment of cancer as well as the fight against aging. Our work is directed at unraveling the role of caveolin-1 as a novel mediator of cellular senescence. Caveolin-1 is the structural protein component of caveolae, invaginations of the plasma membrane involved in signal transduction. Caveolin-1 acts as a scaffolding protein to concentrate, organize, and functionally modulate signaling molecules within caveolar membranes. Our laboratory was the first to demonstrate that caveolin-1 plays a pivotal role in oxidative stress-induced premature senescence. We found that oxidative stress upregulates caveolin-1 protein expression through the p38 MAPK/Sp1-mediated activation of the caveolin-1 gene promoter. We also demonstrated that upregulation of caveolin-1 protein expression promotes premature senescence through activation of the p53/p21Waf1/Cip1 pathway by acting as a regulator of Mdm2, PP2A-C, TrxR1 and Nrf2. Moreover, we found that caveolin-1-mediated premature senescence regulates cell transformation and contributes to cigarette smoke-induced pulmonary emphysema, directly linking caveolin-1's function to age-related diseases. Taken together, our findings indicate that caveolin-1 plays a central role in the signaling events that lead to cellular senescence. Our current main research interest is the identification, at the molecular level, of novel signaling pathways that link caveolin-1 to oxidative stress-induced premature senescence and the characterization of their relevance to aging and age-related diseases using both cellular and animal models. These investigations will provide novel insights into the cellular and molecular mechanisms underlying aging and cancerous cell transformation and will identify novel molecular targets that can be exploited for the development of alternative therapeutic options in the context of age-related diseases, including cancer.

Research Interests and Keywords
  • age-related disease
  • Aging
  • Cancer
  • Caveolin
  • Oxidative Stress
  • senescence
Read More about Ferruccio Galbiati
Madhavi Ganapathiraju

Madhavi Ganapathiraju

Program: Cancer Biology

412-648-9331 madhavi@pitt.edu 5607 Baum Boulevard
Room 522
Pittsburgh PA
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Vanathi Gopalakrishnan

Vanathi Gopalakrishnan

Program: Cancer Biology

Summary

Dr. Gopalakrishnan is a tenured associate professor of biomedical Informatics. Her primary research focus over the past two decades has been on biomarker discovery from multiple types of biomedical data via novel integrative modeling using hybrid machine learning methods being developed and tested in her lab. She is fundamentally interested in technologies for data mining and discovery that allow incorporation of prior knowledge.  Her lab has applied novel variants of rule learning techniques for biomarker discovery, prediction and monitoring of diverse diseases including neurodegenerative and cardiovascular diseases, lung, breast and esophageal cancers, and parasitic infectious disease such as Helminths. Multiple types of 'omic' data obtained from genomics, proteomics, metabolomics and microbiome profiling have been analyzed, leading to insights regarding biomarkers and molecular mechanisms that underlie chronic disease. Biomarkers for early detection of lung and esophageal cancers have been validated across institutional studies. Dr. Gopalakrishnan was a co-leader of the Bioinformatics and Biostatistics core for a decade as part of the NCI-funded Lung SPORE project. She also was the first formal director of the CoSBBI (Computer Science, Biology, and Biomedical Informatics) program which now forms a core part of the Hillman Academy that trains rising high school juniors and seniors in cancer related STEM research.

Dr. Gopalakrishnan also served recently as the director of the Intelligent Systems Program in the School of Computing and Information, which is a highly selective multidisciplinary applied AI graduate degree program at the University of Pittsburgh.

Read More about Vanathi Gopalakrishnan
Sarah Hainer

Sarah Hainer

Program: Cancer Biology

(412) 624-6164 sarah.hainer@pitt.edu 527 Langley Hall
4249 Fifth Ave
Pittsburgh PA
Summary

My research interests focus on the similarities and differences in chromatin structure among different cell types and how chromatin remodeling factors that modulate these differences regulate cell fate. The longterm goals of my laboratory are to comprehensively understand the functions, targets, regulation, and mechanisms of action of non-coding RNAs (ncRNAs) and chromatin regulatory factors with critical functions in the embryonic stem (ES) cell gene regulatory network, through development, and in disease states. Active research areas in my laboratory include: (1) identifying chromatin remodelers that regulate ncRNA expression; (2) determining the function of two uncharacterized classes of ncRNAs in ES cells; (3) characterizing molecular changes occurring in cancer cell lines with chromatin remodeler mutations; (4) optimizing and expanding the utilization of a novel technique for profiling chromatin binding proteins, CUT&RUN. Enabling these studies, my research spans the disciplines of genomics, cell and molecular biology, biochemistry, and genetics.

Read More about Sarah Hainer
Gerry Hammond

Gerry Hammond

Program: Cancer Biology

(412) 383-2215 ghammond@pitt.edu 3500 Terrace St
S327 BST-S
Pittsburgh PA
Summary

Activation of the PI3K pathway, through either oncogenic mutations or loss of tumor suppressors, is arguably the most prevalent transforming event in cancer. Much effort has focused on inhibitors of these pathways, but success to date has been tempered by on-target adverse effects driven by normal physiology that also relies on intact PI3K signaling. My research focuses on the regulatory and homeostatic mechanisms that control PI3K signaling at the level of its central lipid messengers. We aim to uncover how these lipid signals selectively couple to defined signaling outcomes; this basic knowledge will be transformative in predicting how oncogenic PI3K signaling can be selectively targeted while sparing normal physiology.

My lab employs innovative single-cell biochemistry approaches to study lipid signaling in living cells, employing a range of optical biosensors along with gene editing, optogenetic and chemigenetic tools. This approach uniquely empowers us to precisely edit and control cell signaling pathways to model physiology and disease alterations: we can dissect changes away from upstream and downstream pathway components, and notably mimic the effects of potential small-molecule modulators.

Read More about Gerry Hammond
Nadine Hempel

Nadine Hempel

Program: Cancer Biology

(412) 648-4822 nah158@pitt.edu The Assembly
5051 Centre Ave
Pittsburgh PA
Summary

Dr. Hempel's research aims to better understand molecular mechanisms that regulate metastasis and tumor progression, with the ultimate goal of identifying novel targets for therapy of advanced-stage disease. Her research efforts have specifically focused on mechanisms by which tumor cells adapt to stress and her past research on the mitochondrial superoxide dismutase SOD2 has significantly contributed to the understanding that antioxidant enzymes have dichotomous roles during tumor progression. Dr. Hempel’s current research efforts focus on ovarian cancer, which remains the deadliest gynecologic malignancy due to its late-stage diagnosis when significant peritoneal metastatic spread has already taken place, high rates of recurrence and chemoresistance development. Currently, Dr. Hempel’s research group uses a variety of molecular, cellular, imaging, and in vivo techniques to focus on several research areas in ovarian cancer biology, including 1. elucidating the regulation and role of antioxidant enzymes and reactive oxygen species in metastatic tumor cells; 2.identifying novel regulators of anoikis resistance during transcoelomic metastasis; and 3. studying the regulation of mitochondrial fission/fusion and mitochondrial metabolism during ovarian cancer progression.

Read More about Nadine Hempel
Dennis Hsu

Dennis Hsu

Program: Cancer Biology

(412) 623-1722 hsudj@upmc.edu Hillman Cancer Center Research Pavilion
5117 Centre Avenue, Lab 1.20
Pittsburgh PA
Summary

I am a physician-scientist whose research efforts have focused specifically on codon usage, tRNA biology, and amino acid metabolism in colorectal and gastric cancers. Using a combination of computational modeling and wet-lab experiments, I found that amino acid availability directly influences tRNA availability and gene expression in a codon-dependent manner, and also potentially affects the evolution of the cancer genome. I plan to better dissect the contribution of the tumor microenvironment towards nutritional stress of cancer cells as well as determine how tRNA synthetases contribute to survival under starvation conditions.

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Dennis Kostka

Dennis Kostka

Program: Cancer Biology

Summary

How do different organs and tissues arise? What are the genetic and epigenetic mechanisms that drive this development? To address these questions, we design statistical methods and algorithms and apply them to large-scale, genome-wide data. Ultimately, our goal is to generate, test, and confirm hypotheses that are relevant to human health. Current projects include methods for biology at single cell resolution, disease-specific variant prioritization through non-coding regulator loci, and embryonic development of the heart and eye.

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Adrian Lee

Adrian Lee

Program: Cancer Biology

412-641-7557 leeav@upmc.edu The Assembly
5051 Centre Ave
Pittsburgh PA
Summary

The laboratory studies the molecular basis of breast cancer development and resistance to therapy, with the goal to improve precision medicine and outcomes for breast cancer patients. The laboratory employs a systems biology approach, utilizing a combination of single cell and bulk sequencing, computational methods, and biological models to identify and validate new drivers and therapeutic targets. Hypotheses are tested in vitro and in vivo and then moved to clinical trials. The majority of studies incorporate analysis of human specimens, in collaboration with a large network of clinicians and nurses. This includes computational analysis and modeling of large biomedical and genomic datasets including electronic health record data. A major goal is new model development including patient-derived organoids and patient-derived xenografts. A major focus of the laboratory is identifying mechanisms of resistance to endocrine therapy, and new approaches to blocking breast cancer metastasis through precision medicine. This includes the study of estrogen receptor (ESR1) mutations and fusions and synergism with growth factor pathways. Methods include liquid biopsies and use of a rapid autopsy program,. A special focus is on the understanding of invasive lobular cancer (ILC), the second most common but understudied histological subtype of breast cancer. The laboratory has a very strong training environment, with attention to diversity and inclusion and each individuals’ successful career development. One of the top priorities is to maintain a healthy lab environment, ensuring high productivity and rigor.

Research Interests and Keywords
  • Breast Cancer
  • estrogen receptor
  • growth factor signaling
  • insulin-like growth factor
  • progesterone receptor
  • steroid receptors
  • tumor heterogeneity
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Robin Lee

Robin Lee

Program: Cancer Biology

412-648-8607 robinlee@pitt.edu 3083 Biomedical Science Tower 3
3501 Fifth Ave
Pittsburgh PA
Summary

We use live-cell experiments and mathematical models to understand how single cells process information in inflammatory diseases and cancer. To decide between irreversible cell fates such as growth, differentiation or death, cells process information about their environment through a network of molecular circuits. Our research combines principles of systems and synthetic biology with large-scale data to understand how information flows through these circuits. By observing input-output relationships in the same cell using microfluidics, live-cell dynamics and single-molecule microscopy, we aim to decode the ‘language’ of signaling dynamics and develop mathematical models of information flow with single-cell resolution. Our ultimate goal is to understand how population-level responses emerge from single-cell heterogeneity and to rationally manipulate cell fate decisions in disease.

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Gang Li

Gang Li

Program: Cancer Biology

Summary

The main research interest in Dr. Gang Li's lab is to understand the molecular mechanisms underlying the contribution of disease-associated, non-coding functional SNPs to aging-related diseases by focusing on Alzheimer's disease and atherosclerosis. Dr. Li's lab has developed multiple techniques such as Reel-seq, SNP-seq, FREP/SDCP-MS and AIDP-Wb to identify the causal SNPs as well as the SNP-bound regulatory proteins based on genome wide association studies (GWAS). The lab's goal is to use human genetics (GWAS) as a guide to identify new drug targets and, ultimately, to apply these findings to develop allele-specific precision drugs for aging-related human diseases as well as other diseases.

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Xinghua Lu

Xinghua Lu

Program: Cancer Biology

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Antony MichealRaj

Antony MichealRaj

Program: Cancer Biology

(412) 707-3831 micheala@pitt.edu Scaife Hall, 5th Floor, A526/7B
3550 Terrace Street
Pittsburgh PA
Summary

Brain Tumor Metabolism and Functional Cancer Genomics Laboratory
Laboratory of brain tumor metabolism and functional cancer genomics laboratory are established and directed by Dr. Antony MichealRaj in September 2021 at the Department of Neurological Surgery, University of Pittsburgh School of Medicine.
We are focused on exploring the underlying disease mechanism of pediatric brain tumors, with a specific interest in pediatric cancer stem cells- brain tumor metabolism and epigenetics and post transcriptional and translational regulation. Our team is investigating following major themes in pediatric ependymomas and gliomas:
1) Functional cancer genomics using in vivo and In vitro CRISPR screens
2) Metabolic dependencies and epigenetic regulation in primary and recurrent tumors
3) Unraveling the crosstalk between cell signaling and epigenetics
4) mRNA regulation and translational control

Since September 2021, the Brain Tumor Metabolism and Functional Cancer Genomics Laboratory explored the molecular network and metabolic dependencies which are essential for pediatric supratentorial ependymomas survival and proliferation. Supratentorial ependymomas (ST-EPNs) are aggressive pediatric forebrain malignancies, which account for 40% of all intracranial ependymomas. Recurrent fusion of ZFTA (previously known as C11orf95) with RELA or other genes such us YAP1, MAML2, MAML3, NCOA2 are identified to be oncogenic drivers of Supratentorial ependymoma which does not have an effective therapeutic option. Up to 40% of children with this Ependymoma succumb to their disease, and survivors are often left disabled because of toxicity from the tumor and treatment. We have made reasonable progress on identifying the abnormal gene elements that could potentially drive this lethal tumor. However, we are still far behind in understanding the molecular network which makes children vulnerable to this tumor. Unraveling this network is very important for novel therapeutic interventions. We have developed disease models from supratentorial ependymoma patients and applied cutting- edge scientific tools to target one gene at a time on a genome-wide scale. In parallel, we have profiled the surgical biopsies abnormal gene expression and protein levels. Through these analyses, we have identified genes that are not mutated but are very important for tumor development. This essential genetic network unraveled the potential cell of origin and suggest the putative oncogenic route of this neoplasm. Additionally, our metabolic profiling and tracing studies in disease models identified the nutrient demand that are required for epigenetics, macromolecular synthesis and bioenergetic processes in supratentorial ependymomas. We are now exploring single and combined therapeutic approaches to target this tumor by blocking the metabolic activity by selective and blood brain penetrant small molecules and nutrient limited- diet. For the first time, we established a transgenic mouse model for supratentorial ependymoma which will be used as primary tool for investigating disease mechanism and novel therapeutic discoveries/validations.
Our team using patient-derived disease models (Cell lines, Xenografts) and transgenic mouse models and cutting edge next-generation genomic technologies (Bulk and single cell sequencing, ChIP seq, long read sequencing), metabolomics (total and targeted), genetic engineering tools (Genome-wide and focused CRISPR screen) to advance our existing knowledge on pediatric brain tumors and probe novel therapeutic options.

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Satdarshan Monga

Satdarshan Monga

Program: Cancer Biology

smonga@pitt.edu S400 BST South
200 Lothrop Street
Pittsburgh PA
Summary

Dr. Monga is the UPMC Endowed Chair for Experimental Pathology at the University of Pittsburgh, School of Medicine. He is a Professor of Pathology and Medicine and the Associate Dean of Research for the School. He is the Executive Vice Chair of Pathology and the Chief of the Division of Experimental and Translational Pathology. He is the inaugural Director of the Pittsburgh Liver Institute and also the founding Director of P30 funded Pittsburgh Liver Research Center (PLRC), which is 1 of the 17 NIDDK-funded Digestive Disease Research Core Centers and only 1 of the 3 with exclusive liver focus. He also runs a T32 funded training program in Regenerative Medicine. He is an academic physician and has focused on elucidating the cellular and molecular underpinnings of liver injury, repair, and liver cancer for more than 22 years and has been consistently funded by NIH and sponsored research agreements from industry throughout his career. He has published 208 articles, received numerous research and mentoring awards and served on boards of both industry and academia. He has made seminal contributions in this area especially in the understanding of the role of complex signaling pathways such as the Wnt, Hippo and others and several of his findings are now on the verge of being translated into patients. 

There are two major research themes within his laboratory. The first focus is in the broad area of liver physiology. This includes the areas of hepatic development, liver regeneration (following surgical resection, drug-induced injury or cholestasis) and metabolic zonation (division of labor within liver lobule). His work has elucidated the cell-molecule circuitry of liver regeneration following hepatectomy showing Wnt2 and Wnt9b release from endothelial cells to activate -catenin in hepatocytes to induce proliferation and regain of hepatic mass.  His work also showed an important role of -catenin in hepatoblast proliferation during development and then in hepatocyte maturation. In adult liver, his group has shown that Wnt2-Wnt9b from endothelial cells also control gene expression in hepatocytes located in pericentral region of the liver lobule and hence plays an important role in metabolic zonation. He showed an important redundancy between β-catenin and β-catenin at adherens junction where loss of any one of the two catenins was compensated by the other, whereas dual loss in hepatic epithelial or ‘hepithelial’ cells, led to disruption of blood bile barrier and excessive morbidity. The second major focus in the lab has been on understanding the role of β-catenin gene mutations in liver tumors especially hepatoblastoma and hepatocellular cancer. Since mutations in CTNNB1 are observed in 26-38% of all HCC patients, he has generated very relevant mouse models that represent subset of human HCC using sleeping beauty transposon/transposase and crispr/cas9. These models have lent themselves well to help understand the cooperation of mutant CTNNB1 with other oncogenes such as MET, NFE2L2, YAP and others. Their studies have revealed β-catenin to be a driver mutation whose therapeutic targeting may have a profound impact on the field. They have identified addiction of -catenin gene mutated HCCs to mTORC1 due to excess glutamine production by these tumors, as well as resistance to immune checkpoint inhibitors due to unique biology that leads to dearth of immune cell infiltration within the tumor microenvironment. Several discoveries from his lab are now ready to be translated into the clinic and may have both diagnostic and therapeutic implications.

Research Interests and Keywords
  • EGF
  • growth factors
  • hepatic physiology
  • Hepatocellular carcinoma
  • HGF/Met
  • Liver cancer
  • liver development
  • liver disease
  • PDGF
  • Signal Transduction
  • Wnt/beta-catenin
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Steffi Oesterreich

Steffi Oesterreich

Program: Cancer Biology

oesterreichs@upmc.edu The Assembly
5051 Centre Ave
Pittsburgh PA
Summary

The main interest of Dr. Oesterreich's laboratory is to further our understanding of hormone action in women's cancers (including both breast and ovarian cancers), with the ultimate goal to use this knowledge for improved diagnosis and endocrine treatment. These studies include many aspects of translational breast cancer research utilizing basic biochemistry, molecular and cell biology, and cell lines, mouse models and clinical samples. Over the last few years, Dr. Oesterreich has developed a strong research interest in in situ and invasive lobular disease, the second most common yet understudied histological subtype of breast cancer. In her role as Director of Education at the Women's Cancer Research Center, Dr. Oesterreich is also very interested in providing outstanding training opportunities to the next generation of women's cancer researchers.

Research Interests and Keywords
  • bone metastases
  • Breast Cancer
  • Chromatin
  • coregulators
  • Epigenetics
  • estrogen receptor
  • invasive lobular carcinoma
  • lobular carcinoma in situ
  • mutations
  • ovarian cancer
Read More about Steffi Oesterreich
Hatice Osmanbeyoglu

Hatice Osmanbeyoglu

Program: Cancer Biology

412-623-7789 osmanbeyogluhu@pitt.edu UPMC Hillman Cancer Center Research Pavilion
Suite G27c, 5117 Centre Ave.
Pittsburgh PA
Summary

Our group's primary focus is on developing integrative machine learning approaches for extracting therapeutic and biological insights from highly heterogeneous omic datasets, clinical and drug response data, with the purpose of advancing precision medicine. Our projects span across the following areas: 

  • Cancer Genomics: Leveraging machine learning techniques to analyze genomic data from cancer patients, identifying genetic mutations, biomarkers, and potential therapeutic targets for personalized cancer treatment.
  • Single Cell and Spatial Omics: Developing statistical methods for single-cell multi-omics integration, integrating data from different omic layers (such as genomics, proteomics, transcriptomics, epigenomics) to gain a comprehensive understanding of cellular processes and disease mechanisms.
  • Epigenetics: Studying how epigenetic modifications influence an individual's response to different drugs, integrating epigenetic data with clinical information to develop predictive models for personalized drug selection.

Our projects are executed through multi-disciplinary collaborations, recognizing that precision medicine requires expertise from various domains. By leveraging machine learning and integrating diverse datasets, our aim is to contribute to the advancement of precision medicine, ultimately leading to more targeted and effective treatments for patients.

Research Interests and Keywords
  • cancer epigenetics
  • Computational oncology
  • Omics approaches in immunology and immunotherapy
Read More about Hatice Osmanbeyoglu
Andrey Parkhitko

Andrey Parkhitko

Program: Cancer Biology

(339) 368-4594 aparkhitko@pitt.edu Bridgeside Point 1, Room 569
100 Technology Drive
Pittsburgh PA
Summary

My current cancer-related research is focused on i) RB1 tumor suppressor and ii) nutrient interventions that may suppress tumor growth.

RB1 is a tumor suppressor gene that is inactivated in a significant proportion of all cancer cases. A therapeutic approach that specifically targets defects in this tumor suppressor is currently not available. A synthetic lethal (SL) interaction occurs between two genes when the inactivation of either gene alone is viable but the inactivation of both genes simultaneously results in the loss of viability. My lab uses a cross-species approach to identify evolutionarily conserved SL targets for RB1-deficient cells. Our focus is to translate our findings from Drosophila screening and from bioinformatics analysis of human cancer cell lines and human cancer patients into appropriate mouse cancer models and ultimately in a clinical trial in human cancer patients.

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Laura Pascal

Laura Pascal

Program: Cancer Biology

(412) 623-3916 lep44@pitt.edu Shadyside Medical Building
4200 Centre Ave, Suite G34
Pittsburgh PA
Summary

Prostate cancer and benign prostatic hyperplasia are two diseases which present a significant burden for older men in the US. Although BPH is not usually life-threatening, the mechanisms contributing to BPH are largely unknown which makes it difficult to develop successful BPH prevention and treatment strategies. My research focus is developing and characterizing animal models of BPH and prostate cancer as powerful tools for measuring efficacy of small molecules designed to inhibit androgen receptor function in prostate cancer and of 5ARI and COX-2 inhibitors to reduce prostatic inflammation and improve bladder function in BPH.

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Edward Prochownik

Edward Prochownik

Program: Cancer Biology

(412) 692-6795 procev@chp.edu Rangos Research Center, Room 5124
Children’s Hospital of Pittsburgh, 4401 Penn Ave.
Pittsburgh PA
Summary

 Dr. Prochownik is interested in cancers resulting from the de-regulated expression of the c-Myc oncoprotein. He is using animal models of pediatric and adult liver cancer (hepatoblastoma and hepatocellular carcinoma) to ascertain the molecular, biochemical and metabolic changes that accompany tumor progression, regression and recurrence. He is utilizing over-expression and knockout models to determine how genes that cooperate with or are affected by Myc such as ChREBP and pyruvate dehydrogenase specifically contribute to the metabolic and molecular landscapes of these tumors.

Research Interests and Keywords
  • c-Myc
  • Molecular oncology
  • tumor metabolism
  • tumor suppressors
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Sadeesh Ramakrishnan

Sadeesh Ramakrishnan

Program: Cancer Biology

412-648-4293 Ramaks@pitt.edu W1057 Biomedical Science Tower
200 Lothrop Street
Pittsburgh PA
Summary

Non-alcoholic fatty liver (NAFLD)-related HCC develops without liver cirrhosis and alcohol consumption. Perturbations in liver lipid disposal pathways, in particular dysregulation of hepatic ketogenesis, contributes to the pathogenesis of NAFLD and fibrosis. Conversely, ketogenic diet (KD) supplementation decreases liver lipid accumulation, inflammation, and fibrosis in NAFLD models. Our lab is interested in understanding how ketone bodies or ketogenesis regulate NAFLD-related HCC. We have liver specific ketogenesis insufficient and ketolysis insufficient mice to test our hypothesis.

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Partha Roy

Partha Roy

Program: Cancer Biology

Summary

The overall research focus of the Roy laboratory is studying the role of actin-binding proteins and actin-regulated transcription factors in physiological and pathological events. Specific focus areas are actin-binding proteins (profilin, Ena/VASP) and their regulation, MRTF-SRF transcriptional axis, fundamental mechanisms of cell migration, cancer biology (breast and renal cancer), cell signaling, vascular-immune cell crosstalk, and angiogenesis (in both developmental and pathological settings). We seek to a.) understand molecular mechanisms of various aspects of cancer metastasis, regulation of tumor microenvironment and therapy response of cancer cells, and b.) Discover novel therapeutic agents. Our laboratory uses a variety of experimental approaches including CRISPR/RNAi, protein-protein interactions, 2D gel electrophoresis, genetically engineered mouse models of cancer and angiogenesis, mouse models of atherosclerosis, tumor xenografts, metastasis assays, in vitro, ex vivo and in vivo angiogenesis assays, functional genomics and proteomics, live-cell imaging at single cell level, computationally-guided small molecule screening and bioinformatics.

Research Interests and Keywords
  • Actin Cytoskeleton
  • angiogenesis
  • Breast Cancer
  • cell migration
  • Metastasis
  • Renal cancer
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J. Peter Rubin

J. Peter Rubin

Program: Cancer Biology

Summary

Dr. Rubin is a noted expert on adult stem cells derived from fat tissue and advanced reconstructive surgery. Dr. Rubin leads a program that is devising innovative strategies for the use of adipose (fat)-derived stem cells to not only address problems of tissue regeneration but also other diseases that benefit from stem cell-based therapies. He is co-director of the Adipose Stem Cell Center and co-director of the UPMC Aesthetic Plastic Surgery Center. His laboratory research focuses on applications of adult adipose-derived stem cells for restoring damaged tissues after trauma and cancer therapy. He currently is the lead investigator for clinical trials using technologies designed to improve the lives of wounded military personnel. He recently founded and directs the Center for Innovation in Restorative Medicine at the University of Pittsburgh Medical Center, an advanced clinical accelerator unit with expertise in regulatory affair, preclinical testing, and clinical trials design and management.

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Jonathan Silverstein

Jonathan Silverstein

Program: Cancer Biology

412-624-8950 j.c.s@pitt.edu Department of Biomedical Informatics
Room 433, 5607 Baum Boulevard, Suite 500
Pittsburgh PA
Summary

Jonathan Silverstein, MD, MS, FACS, FACMI, serves as Chief Research Informatics Officer and Professor of Biomedical Informatics at University of Pittsburgh School of Medicine. He is internationally known for his expertise, and federally funded research, in the application of advanced computing architectures to biomedicine and on the design, implementation and evaluation of high-performance collaboration and visualization environments for anatomic education and surgery. 

Research Interests and Keywords
  • Clinical Informatics
  • Imaging/Visualization/Virtual Reality
  • Learning Health Systems
  • oncology informatics
  • Virtual Organizations
  • Vocabularies
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Aatur Singhi

Aatur Singhi

Program: Cancer Biology

(412) 864-1508 singhiad@upmc.edu 200 Lothrop Street
Room A616.2
Pittsburgh PA
Summary

Dr. Singhi's current research focus is primarily translational in the area of gastrointestinal, pancreatic, hepatobiliary and peritoneal pathology, and can be summarized in the following areas:

(1) Clinical diagnostic test development. In conjunction with other members of pathology, gastroenterology, surgical oncology and radiology, Dr. Singhi has been involved in the development of multiple clinical diagnostic tests for the evaluation of pancreatic cysts, biliary strictures, neuroendocrine tumors, and early detection of neoplasms involving the hepatopancreatobiliary tract. His research is supported by grants from the Pancreatic Cancer Action Network (PanCAN), National Pancreas Foundation (NPF), the University of Pittsburgh and the Institute for Precision Medicine (IPM) at the University of Pittsburgh. For more information regarding such tests as PancreaSeq (pancreatic cysts), BiliSeq (biliary strictures) and PanNeuroSeq (pancreatic neuroendocrine neoplasms), please refer to the Molecular & Genomic Pathology Laboratory website: http://mgp.upmc.com.

(2) Pathologic evaluation of non-neoplastic pancreatic pathology. In collaboration with several investigators, Dr. Singhi is involved in a multi-institutional effort to characterize various non-neoplastic pancreatic diseases, such as genetically and environmentally associated chronic pancreatitis.

(3) Co-director of the Biospecimen Repository and Processing Core (BRPC) of the Pittsburgh Liver Research Center (PLRC): http://livercenter.pitt.edu. Histopathologic and genetic characterization of peritoneal mesothelioma. In conjunction with members of the Division of Thoracic Pathology, Molecular & Genomic Pathology, and Surgical Oncology, Dr. Singhi's team has identified the genetic landscape of peritoneal mesothelioma with the goal of identifying biomarkers for prognostication and treatment stratification of patients.

(4) The epigenetic pathogenesis of pancreatic neuroendocrine tumors. In collaboration with investigators at the UPMC Division of Gastroenterology, Hepatology and Nutrition, and UPMC Hillman Cancer Center. This represents an international observational trial to evaluate prognostic biomarkers for pancreatic neuroendocrine tumors and determine the underlying epigenetic pathogenesis of these increasingly prevalent neoplasms.

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Alexander Sorkin

Alexander Sorkin

Program: Cancer Biology

sorkin@pitt.edu 3500 Terrace Street
S368 Biomedical Science Tower (South)
Pittsburgh PA
Summary

The focus of the research in the laboratory is currently split into two major directions which are apparently distinct from each other with respect to the biological systems involved, their relation to the human disease, and experimental models used. However, the main idea underlying both directions is conceptually the same - to understand how endocytosis and post-endocytic trafficking regulates function(s) of the transmembrane proteins, such as receptors and transporters.

The first direction is the elucidation of the molecular mechanisms of endocytosis of growth factor receptors using a prototypic member of the family, epidermal growth factor (EGF) receptor, and analysis of the role of endocytosis in spatial and temporal regulation of signal transduction by the EGF receptor. The second direction is elucidating the role of trafficking processes in the regulation of dopaminergic neurotransmission by the plasma membrane dopamine transporter (DAT).

Research Interests and Keywords
  • EGF Receptor
  • Endocytosis
  • head and neck cancer
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Laura Stabile

Laura Stabile

Program: Cancer Biology

412-623-7821 las22@pitt.edu Hillman Cancer Center
5117 Centre Avene Lab 2.7
Pittsburgh PA
Summary

Dr. Stabile's laboratory is focused on the role of growth factors and hormones in the development of non-small cell lung cancer. Estrogen receptor signaling has been shown to be important in inducing proliferation in lung tumor preclinical models as well as promoting aggressive disease in lung cancer patients. We have demonstrated both genomic and non-genomic effects of estrogen in the lung and have elucidated cross-talk between the estrogen signaling pathway and multiple growth factor pathways including epidermal growth factor receptor, fibroblast growth factor receptor, hepatocyte growth factor and vascular endothelial growth factor. These preclinical studies have led to clinical trials examining the effectiveness of the anti-estrogen fulvestrant combined with targeted therapies for advanced stage lung cancer. Current interests include: 1) examining the mechanistic link between inflammation and estrogen signaling in lung carcinogenesis; 2) identification of dietary factors that modify lung cancer risk; and 3) development of novel therapeutic and prevention strategies involving hormonal manipulation and/or anti-inflammatory therapies in select high-risk populations.

Research Interests and Keywords
  • epidermal growth factor receptor
  • Estrogen
  • estrogen receptor
  • fibroblast growth factor receptor
  • Hepatocyte Growth Factor
  • Hormones
  • Lung Cancer
  • Signal Transduction
  • targeted cancer therapies
  • Vascular Endothelial Growth Factor
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Wayne Stallaert

Wayne Stallaert

Program: Cancer Biology

(919) 579-2798 stallaert@pitt.edu The Assembly, Office 1033
5051 Center Ave
Pittsburgh PA
Summary

Cell cycle dysregulation is a hallmark of every tumor. My lab uses quantitative single-cell microscopy and machine learning to study how the cell cycle changes during tumorigenesis, metastasis, and drug treatment, and the role of tumor microenvironment in regulating the proliferative state of a patient's tumor. Ultimately, our goal is to predict disease outcomes and therapeutic success by looking directly at the phenotype driving tumor growth — the cancer cell cycle. 

Research Interests and Keywords
  • Breast Cancer
  • Cell Cycle
  • Machine learning
  • Metastasis
  • Microscopy
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Richard Steinman

Richard Steinman

Program: Cancer Biology

steinman@pitt.edu UPMC Cancer Pavilion
5150 Centre Avenue
Pittsburgh PA
Summary

Dr. Steinman has interrogated the function and regulation of cdk inhibitors during quiescence and differentiation. His recent research focuses on the contribution of platelets to tumorigenesis and on potential platelet-based urinary biomarkers of treatment efficacy. He also oversees three programs involving over 190 physician scientist trainees and conducts related educational research.

Research Interests and Keywords
  • Breast Cancer
  • Physician Scientist Education
  • Platelets
  • Tumor Microenvironment
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Gary Thomas

Gary Thomas

Program: Cancer Biology

Summary

We investigate signaling pathways that integrate membrane traffic with the regulation of homeostasis and the onset of disease, including cancer and autism, and we leverage these discoveries to develop targeted therapies. Our studies are grounded by our discovery of the PACS family of multi-functional sorting proteins. Currently, we are investigating how the PACS proteins regulate key deacetylases, including SIRT1 and HDAC6, to control signaling pathways impacting cancer cell death, obesity, and neurodevelopmental disorders. 

Research Interests and Keywords
  • HDAC6
  • Mitochondria
  • p53
  • SIRT1
  • TRAIL
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Mohamed Trebak

Mohamed Trebak

Program: Cancer Biology

(518) 986-3733 trebakm@pitt.edu Biomedical Science Tower Office E1355
200 Lothrop Street
Pittsburgh PA
Summary

I am an ion channel physiologist with long term interests in basic ion channel regulation and activation and the contributions of altered channel function to disease. I have been funded all my career by NHLBI, NIA and NIEHS and have developed strong interests in the contribution of ion channel dysfunction to cellular, molecular and metabolic remodeling in vascular proliferative diseases and lung obstructive diseases. Nevertheless, I have consistently maintained an interest in the nascent and exciting field of "ion channels and cancer". I have consistently had one postdoc (sometimes two) working on ion channel dysregulation in breast and colon cancer and glioblastomas and we have published several influential papers on the subject.

Research Interests and Keywords
  • Calcium Signaling
  • colorectal cancer
  • Mitochondrial Calcium
  • Receptor Signaling
  • Store-Operated Calcium Entry
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George Tseng

George Tseng

Program: Cancer Biology

Summary

Dr. George Tseng is Professor and Vice Chair for Research in the Departments of Biostatistics, School of Public Health, University of Pittsburgh. He also has secondary appointments in Human Genetics, and Computational and Systems Biology. He received BS (1997) and MS (1999) in Mathematics from the National Taiwan University under Dr. Hung Chen, and ScD (2003) in Biostatistics from the Harvard School of Public Health under Dr. Wing Hung Wong's lab. He joined Pitt since 2003 and leads a research group in Bioinformatics and Statistical Learning. His research interests focus on statistical modeling and applications for -omics and bioinformatic problems to improve precision medicine and human health. His research group has published 90+ methodological/major papers and 115+ collaborative papers (as of Mar 2023), in addition to co-invention of 5 patents. He has received multiple awards, including ASA Fellow, Statistician of the Year (ASA Pittsburgh Chapter), and Provost's Award for Excellence in PhD Mentoring (University of Pittsburgh). Collaboration with biological and clinical labs plays an important role where most of his projects and methodological ideas come from. 

Dr. Tseng has actively served in the statistical community, including President of ASA Pittsburgh Chapter in 2014-2017 (President-Elect, President and Past-President), Chair of ASA Section on Statistics in Genomics and Genetics (SSGG) in 2023-2025 (Chair-Elect, Chair and Past-Chair), and Board of Directors of International Chinese Statistical Association (ICSA) in 2024-2026.

Research Interests and Keywords
  • Bioinformatics
  • Cancer Computational Biology
  • Statistical Machine Learning
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Shikhar Uttam

Shikhar Uttam

Program: Cancer Biology

(412) 623-7986 shf28@pitt.edu Hillman Cancer Center Research Pavilion
5117 Centre Ave, Rm 2.6f
Pittsburgh PA
Summary

Our research focuses on understanding the cancer systems biology of the tumor microenvironment. We are interested in studying how different cell types with varying lineages, and with different signaling and signal processing capabilities come together within the spatial context of the microenvironment to give rise to malignant phenotypes in individual patients, whether they be neoplastic transformation, cancer progression, recurrence, or response to therapy. Our specific interest is in gastrointestinal cancers (GI), particularly colorectal cancer, but we aim to expand our study to other solid tumors. We also work on cancer prognosis in GI patients at risk of developing cancer, for example, patients with inflammatory bowel disease or Barret's esophagus. Our research work utilizes high dimensional microscopy and optical imaging combined with imaging science, mathematical and systems modeling, and data science in general. In this latter context we aim to intelligently incorporate omics data into our research, to better integrate biological understanding with improved patient outcomes.

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Flordeliza Villanueva

Flordeliza Villanueva

Program: Cancer Biology

Summary

Dr. Villanueva's research focuses on the development of medical diagnostic and therapeutic strategies based on ultrasound and ultrasound contrast agents (gas-filled microspheres, or microbubbles). Her work has consistently bridged fundamental imaging sciences with translational biomedical research. As an Established Investigator of the American Heart Association, she has been a leader in the development of microbubbles for the assessment of myocardial perfusion, and ultrasound molecular imaging with targeted microbubbles for the detection of inflammatory and angiogenic endothelial markers in pre-clinical models of heart disease. Dr. Villanueva's lab has pioneered the development and application of microbubbles as molecular probes, and acoustic detection strategies for optimizing imaging sensitivity. Her lab group has applied fundamental principles of ultrasound and the physics of microbubble acoustic behaviors to develop novel targeted molecular therapeutics, whereby nucleic acid loaded microbubbles (siRNA, miRNA, plasmid), in the presence of precisely tuned ultrasound, selectively enhance membrane permeability and deliver payloads to the target site. These studies are conducted at the Center for Ultrasound Molecular Imaging and Therapeutics, a translational multidisciplinary research facility which epitomizes the reciprocal relationship between imaging sciences and biomedical translational research.

Research Interests and Keywords
  • Drug and Gene Delivery
  • Molecular Imaging
  • Ultrasound
  • Ultrasound Contrast Agents
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Xiaosong Wang

Xiaosong Wang

Program: Cancer Biology

412-623-1587 xiaosongw@pitt.edu Hillman Cancer Center, Room G.5a
5117 Centre Ave.
Pittsburgh PA
Summary

The Cancer Genome Project Initiatives have generated a daunting amount of genomic and deep sequencing data for tens of thousands of human tumors. An overarching challenge of this post-genomic era is to identify and recognize the cancer drivers and targets from these big genomic data, especially those that can be therapeutically targeted to improve the clinical outcome. The mission of our lab is to apply a multiple disciplinary approach inclusive of integrative bioinformatics, cancer genetics, molecular cancer biology, and translational studies to identify driving genetic aberrations and appropriate cancer targets on the basis of deep sequencing and genomic profiling datasets. Our research projects are composed of both computational and laboratory components. Our dry lab researches focus on developing innovative and integrative computational technologies to discover causal genetic and epigenetic alternations, viable therapeutic targets, and predictive biomarkers in cancer. In particular, we have innovated a concept signature (ConSig) analysis that employs molecular fingerprints for high-throughput interpretation of the biological function of candidate targets in cancer (Nature biotech 2009). In addition, we have formulated a 'fusion breakpoint principle' that describes the intragenic copy number aberrations characteristic of recurrent gene fusions, thus enabling genome-wide detection of copy number breakpoints generating gene fusions. Based on these principles we further developed a powerful bioinformatics tool called 'Fusion Zoom' that identifies recurrent pathological gene fusions via integrative analyses of RNA sequencing, copy number, and gene concept datasets (Nature Commun 2014). Further, we have discovered the crucial application of ConSig analysis in revealing the primary oncogenes targeted by genomic amplifications, and developed a new integrative genomic analysis called 'ConSig-Amp' to detect viable cancer targets. Moreover we also developed an integrated computational-experimental approach called HEPA-PARSE for the genome-wide detection of clinically important tumor specific antigen (TSA) targets (Cancer Research 2012). Our wet lab researches focus on experimentally characterizing individual genetic and epigenetic aberrations in breast cancer such as recurrent gene fusions, genomic amplifications, and epimutations, as well as qualifying viable cancer targets and predictive biomarkers for the development of precision therapeutics in breast cancer. Our current disease focus is clinically intractable breast cancers, such as luminal B or basal-like tumors. In particular, by applying the FusionZoom analysis to the RNAseq and copy number data from The Cancer Genome Atlas, we have discovered a novel recurrent gene fusion involving the estrogen receptor gene in a subset of breast cancers. This fusion called ESR1-CCDC170 is preferentially present in 6-8% of luminal B tumors -- a more aggressive subtype of estrogen receptor positive breast cancer. To date, this is the first and most frequent gene fusion yet reported in this tumor entity (Nature Commun. 2014). We are now assessing the druggability of this fusion with the goal of developing effective targeted therapy against this genomic target. We expect that our new discoveries will yield novel insights into the recurring genetic abnormalities leading to breast cancer initiation, progression, and therapeutic resistance, and establish viable targets for effective intervention.

Research Interests and Keywords
  • cancer cell biology
  • cancer genetics
  • Cancer genomics
  • integrative bioinformatics
Read More about Xiaosong Wang
Yue Wang

Yue Wang

Program: Cancer Biology

(412) 623-3215 yuw130@pitt.edu Research Pavilion, Suite G1
5117 Centre Ave
Pittsburgh PA
Summary

I am doing cancer research related to molecular biology, genetics, data mining with bioinformatics and immunology. According to immune relationship with cancers, there are hot tumors and cold tumors including immune cells exclusion and immune cell deserts to influence the progress of cancer patients, the "hot" tumors with immune infiltration has more chance for the carriers to get complete response to ICI therapy and chemotherapy. Our T cell migration test followed by flowcytometry showed the TNBC (Triple negative breast cancer) which has gene fusions of BCL2L14ETV6 has more resistant to T cells migration (especially CD8) through different cytokine/chemokine "talk" with T cells. The preliminary data also shows BCL2L14-ETV6 fusions orchestrate immunosuppressive and protumor cytokines contexture and impair immune cell infiltration. In addition, it modulates the target genes of NFkb, a central mediator of inflammation, endows epithelial mesenchymal transition, confers paclitaxel resistance. 

In addition, Low-cost multi-omics sequencing is expected to become clinical routine and transform precision oncology. Viable computational methods that can facilitate tailored intervention while tolerating sequencing biases are in high demand. Here we propose a class of transparent and interpretable computational methods called integral genomic signature (iGenSig) analyses, that address the challenges of cross-dataset modeling through leveraging information redundancies within high-dimensional genomic features, averaging feature weights to prevent overweighing, and extracting unbiased genomic information from large tumor cohorts.we develop a battery of iGenSig models for predicting cancer drug responses, and validate the models using independent cell-line and clinical datasets. The iGenSig models for five drugs demonstrate predictive values in six clinical studies, among which the Erlotinib and 5-FU models significantly predict therapeutic responses in three studies, offering clinically relevant insights into their inverse predictive signature pathways. Together, iGenSig provides a computational framework to facilitate tailored cancer therapy based on multi-omics data. (Nature Communication 2022)

In addition, I am culturing different kinds of T cells and look into potential T cell therapies for cancers in the future. I did T cell repertoire analysis on PBMC from pancreatic cancer patients, which showed the more versatile of T cell repertoire system the better potential response rate from chemotherapy and other therapies. Also, I got some certifications from Lifestyle Medicine which includes 6 pillars of nutrition science, exercise physiology, sleep science, stress management, positive psychology, removal dictation, which can demonstrate to have the potential to reverse some chronic diseases.

Research Interests and Keywords
  • cancer genetics
  • Cancer Molecular Biology
  • Gene Fusion
  • Immunology
  • Lifestyle Medicine
  • T cells
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Zhou Wang

Zhou Wang

Program: Cancer Biology

wangz2@upmc.edu Shadyside Medical Center, Suite G40
5200 Centre Avenue
Pittsburgh PA
Summary

One focus of my lab is to investigate the mechanisms regulating androgen receptor (AR) nuclear localization, particularly androgen-independent AR nuclear localization in castration-resistant prostate cancer (CRPC) which is the second leading cause of cancer death in American men.  AR remains to be the key driver in majority of CRPC tumors resistant to the current AR targeting agents. AR nuclear localization is necessary for its function as a transcription factor. According to the classical model of AR nucleocytoplasmic trafficking, AR is present in the cytoplasm in the absence of androgens, which can be imported into the nucleus in the presence of androgens, and the imported AR will be exported upon androgen withdrawal. However, this model is not supported by our recent discovery that imported nuclear AR is degraded, but not exported, upon androgen withdrawal and that unliganded AR can be also imported and rapidly degraded in the nucleus. These findings promoted us to investigate the mechanism of nuclear-specific AR degradation. Identification and characterization of factors responsible for nuclear-specific AR degradation will allow us to investigate if and how these factors are dysregulated in CRPC cells. In addition, we will continue developing novel AR antagonists, with collaborations with experts in medicinal chemistry and structural biology, to identify and characterize small molecules that can inhibit androgen-independent AR nuclear localization in CRPC.

Research Interests and Keywords
  • Androgen Receptor (AR)
  • Androgen-Independent Activation of AR
  • AR Protein Degradation
  • Castration-Resistant Prostate Cancer (CRPC)
  • Novel AR Antagonists
  • Nucleocytoplasmic Trafficking of AR
  • Prostate cancer
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Kurt Weiss

Kurt Weiss

Program: Cancer Biology

412-802-4137 weiskr@UPMC.EDU UPMC Shadyside Medical Center
5200 Centre Avenue, Suite 415
Pittsburgh PA
Summary

In addition to specializing in pediatric and adult orthopaedic oncology, Dr. Weiss directs a basic science laboratory dedicated to the study of sarcomas ' cancerous tumors that arise in musculoskeletal tissues. As a bone cancer survivor himself, Dr. Weiss brings passion and enthusiasm to the laboratory, clinic, and operating room.

Research Interests and Keywords
  • Orthopaedic oncology
  • Osteosarcoma
  • sarcoma basic biology
  • translational research
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Alan Wells

Alan Wells

Program: Cancer Biology

412-647-7813 wellsa@upmc.edu Scaife Hall, S713
3550 Terrace Street
Pittsburgh PA
Summary

The Wells Laboratory research program, in close collaboration with its research partners, aims to understand cell migration in terms of how motility processes are regulated, and understand how this regulation of migration plays a role in physiologic and pathologic situations. We are integrating the knowledge gained from our biochemical and biophysical mechanistic studies into our investigations concerning conditions of dysregulated (tumor invasion) and orchestrated (wound healing and organogenesis) cell motility. As part of understanding the motility response, we are investigating both how this particular integrated cell response is selected from among others and the metabolic consequences of motility. This integrative approach provides reinforcing insights and novel avenues for exploration into the basic signaling pathways as well as functioning of whole organism. As a model system, we explore motility signaling from the epidermal growth factor receptor (EGFR) in adherent cells. EGFR plays a central role in the functioning in a wide variety of both stromal and epithelial tissues, and is the prototype for other receptors with intrinsic tyrosine kinase activity. Thus, these studies should have widespread implications.

The two central foci are tumor progression and wound repair. In tumor progression, we examine breast and prostate carcinoma invasion and metastases in terms of molecular signals and the special micro-environments. For this, the laboratory uses human tissues, animal models, and a unique 4-dimensional liver microtissue. In would repair, the current model system is skin wound healing, in which the communications between the epidermis, dermis, and blood vessels is parsed at the molecular levels. The role of stem cells in the natural repair process and as a rationale therapeutic is also being investigated. These two areas are re-inforcing as many of the key molecules and cellular processes are part of the generalizable onco-fetal-wound program. 

Research Interests and Keywords
  • Breast Cancer
  • Dormancy
  • Melanoma
  • Metastasis
  • Microphysiologic Systems (MPS)
  • Prostate cancer
Read More about Alan Wells
Jianhua Xing

Jianhua Xing

Program: Cancer Biology

Read More about Jianhua Xing
Da Yang

Da Yang

Program: Cancer Biology

412-383-5145 dyang@pitt.edu 308 Pavilion
Pittsburgh PA
Summary

Da Yang's lab studies cancer pharmacogenomics by integrating bioinformatics and experimental tools. We are specifically focused on identifying novel disease-driving none-coding RNAs (ncRNAs), modeling ncRNA down-stream regulatory network, and characterizing ncRNAs’ function in cancer therapy using in vivo and in vitro cancer models. Our integrative strategy has led to the discovery of novel RNA genes that serve as master regulators of drug resistance in ovarian and breast cancers by regulating EMT (Cancer Cell, 2013) and DNA repair pathway (JNCI, 2015; JAMA, 2011; Theranostics, 2020a). We have successfully built and identified key RNA-targets regulatory network for cancer metastasis and drug resistance (Clin Cancer Res, 2014 and PNAS, 2015; Theranostics, 2020b). Recently, we performed an integrated analysis of the lncRNA-drug interaction landscape and cloned a novel intergenic lncRNA gene that promotes breast cancer tumorigenesis through inhibiting tumor immune response  (Cancer Cell, 2018; Nat Commun, 2018; Science Advances, 2020; Science Advances, 2022). 

Research Interests and Keywords
  • Epigenetics
  • Immunogenomics
  • personalized cancer medicine
  • RNA Biology
Read More about Da Yang
Reza Zarnegar

Reza Zarnegar

Program: Cancer Biology

rezazar@pitt.edu S-411A S-BST
200 Lothrop Street
Pittsburgh PA
Summary

The focus of Dr. Zarnegar’s laboratory is to decipher the molecular mechanisms by which Hepatocyte Growth Factor (HGF) and its receptor MET regulate hepatocyte growth and metabolism. In particular, their focus is on the regulation of hepatic glucose and fat metabolism and its implication in Fatty Liver Disease. Studies are also aimed at exploiting  HGF/MET in chronic liver diseases inflicted by liver inflammation, hepatocyte degeneration and hepatitis such as NASH. Dr. Zarnegar’s laboratory also studies HGF gene mutation in human cancer such as breast, colon, and liver cancer and how to target HGF/MET axis in cancer.

Research Interests and Keywords
  • Hepatocyte Growth Factor (HGF)
  • Liver cancer
  • MET
  • NASH
Read More about Reza Zarnegar
Ioannis Zervantonakis

Ioannis Zervantonakis

Program: Cancer Biology

Summary

Understanding cell behavior in native tumor microenvironments and developing new strategies to deliver therapeutics directly to tumor cells are critical in improving and extending patients’ lives. Our lab employs a quantitative approach that integrates microfluidics, systems biology modeling, and in vivo experiments to investigate the role of the tumor microenvironment on breast and ovarian cancer growth, metastasis and drug resistance. Our goal is to develop bioengineered tumor microenvironment platforms and apply them to improve understanding of tumor-stromal signaling mechanisms in order to: (1) discover biomarkers that guide new drug development and improve prognosis, (2) develop new strategies to improve existing treatment protocols and (3) engineer microfabricated tools that enable screening and personalization of cancer therapies.

Research Interests and Keywords
  • Cancer metastasis
  • Drug Resistance
  • Microfluidics
  • Systems modeling of cell-cell interactions
  • Tumor Microenvironment
Read More about Ioannis Zervantonakis
Margarita Zuley

Margarita Zuley

Program: Cancer Biology|Cancer Biology

zuleyml@upmc.edu Magee-Womens Hospital of UPMC Breast Imaging
300 Halket Street
Pittsburgh PA
Read More about Margarita Zuley

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