Program Members

Co-Leaders

Patricia Opresko

Patricia Opresko

Program: Genome Stability

412-623-7764 plo4@pitt.edu UPMC Hillman Cancer Center Research Pavilion
5117 Centre Avenue, Suite 2.6a
Pittsburgh PA
Summary

My lab studies DNA damage and repair at telomeres. Telomeres are the caps at chromosome ends that are essential for preserving the genome. When chromosomes lose their telomere caps the cells age and this contributes to the onset of degenerative diseases with aging. If chromosomes lose their telomere caps in pre-cancerous cells, then this causes genetic alterations that hasten the progression to cancer. Understanding mechanisms of telomere damage and repair should lead to new intervention strategies aimed at preserving these regions of the genome that are so critical for protecting our chromosomes and maintaining youthful cells. Conversely, we aim to leverage new findings to develop therapeutic strategies that deplete telomeres in cancer cells to prevent them from dividing. 

Read More about Patricia Opresko

View Investigators by Last Name

A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z

Members

Jonathan Alder

Jonathan Alder

Program: Genome Stability

412-624-8681 alderju@upmc.edu BST W1246
200 Lothrop St.
Pittsburgh PA
Summary

My research focuses on understanding the role of telomere length in human health and disease. Telomeres are caps on the ends of each of chromosomes and shorten as we age. All cancer cells must find a way to maintain their telomeres to sustain tumor growth. Our lab investigates mechanisms that tumors use to maintain their telomeres to identify potential targets for therapeutic intervention. We hope these studies will lead to a deeper understanding of how telomere maintenance contributes to cancer pathogenesis and potentially inform rational therapies.

Read More about Jonathan Alder
Karen Arndt

Karen Arndt

Program: Genome Stability

412-624-6963 arndt@pitt.edu A316 Langley Hall
4249 Fifth Ave
Pittsburgh PA
Summary

A fundamental question in molecular biology is how organisms interpret the vast amounts of information encoded in their genomes. The Arndt lab uses a wide range of experimental approaches to study the first step in gene expression, the synthesis of mRNA by RNA polymerase II, with a focus on the mechanisms that regulate transcription in the chromatin environment of a eukaryotic cell.  Specific areas of interest include the mechanisms that couple histone modifications to active transcription, the coordination among different epigenetic modifications and their impact on transcription elongation and termination, and the molecular functions of core RNA polymerase II elongation factors with broad and conserved effects on the eukaryotic transcriptome.  The fundamental importance of understanding eukaryotic transcriptional regulation is evident from the large number of human developmental defects and diseases, including cancer and AIDS, that arise when cellular transcription factors are altered by mutation or commandeered by viral proteins.

Research Interests and Keywords
  • cellular transcription
  • Chromatin
  • Gene Expression
  • mRNA synthesis
  • RNA polymerase II
Read More about Karen Arndt
Christopher Bakkenist

Christopher Bakkenist

Program: Genome Stability

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

Radiation therapy and many chemotherapies induce DNA damage. These therapies work because cancer cells divide more rapidly than normal cells and cancer cells acquire mutations that change their DNA damage responses and DNA repair mechanisms. Nevertheless, radiation and DNA damaging chemotherapies may not generate long-term responses as the dose of DNA damage required to kill all cancer cells may kill too many normal cells – dose limiting toxicity. The Bakkenist Lab studies how pharmacologic DNA damage response inhibitors can be used to increase the damage induced in cancer cells and potentiate anti-tumor immune responses. Our long-term goals are to develop new therapeutic approaches to manage human cancer.

Visit the Bakkenist Lab Website to learn more.

Research Interests and Keywords
  • Cancer pharmacology
  • DNA repair
Read More about Christopher Bakkenist
Miguel Brieno-Enriquez

Miguel Brieno-Enriquez

Program: Genome Stability

Summary

Research in the Brieno-Enriquez lab focuses on the regulation of gametogenesis in human and mouse and, more specifically, the fundamental mechanisms that are required to produce viable germ cells. Our studies include the analysis of all the different stages of germs cells including primordial germ cells (PGCs), spermatocytes, oocytes, as well as how age affects them. Our long-term goal is to test our overarching hypothesis that gene expression, epigenetic clock, and chromatin structure in the naked mole-rat can be hijacked for use in other species, allowing us to regulate the establishment and maintenance of the ovarian reserve, oocyte quality, and reproductive longevity.

Read More about Miguel Brieno-Enriquez
Jeffrey Brodsky

Jeffrey Brodsky

Program: Genome Stability

412-624-4831 jbrodsky@pitt.edu A321 Langley Hall
4249 Fifth Ave
Pittsburgh PA
Summary

Our work focuses on understanding: (1) how misfolded proteins are recognized and destroyed in normal and tumor cells, (2) how molecular chaperones mediate protein quality control “decisions”, (3) how protein quality control pathways can be targeted in disease models, and (4) how cellular stress responses (such as the Unfolded Protein Response, UPR) affect protein biogenesis and homeostasis, especially in cancer. The pursuit of these goals has employed biochemical, cell biological, and genetic tools using a range of models, including yeast, cell culture, and rodents. Our early work contributed to the discovery of the ER associated degradation (ERAD) pathway, which we named, and ongoing studies are deciphering the mechanisms underlying the ERAD pathway in yeast, mammalian cell culture, and rodent models, and its relationship to cellular stress responses. The importance of ERAD is underscored by the fact that >70 human diseases—including several cancers—are associated with this pathway. In parallel, new classes of small molecule modulators of chaperones and the ubiquitin-proteasome pathway have also been isolated, which we have used to probe the relationship between stress responses, protein homeostasis (“proteostasis”), and tumorigenesis. Ongoing work has capitalized on several of our tools and areas of expertise, including (1) an analysis of protein degradation pathways and the ubiquitin-proteasome system in breast and ovarian cancer, (2) the use of small molecules and drugs to target cancer vulnerabilities, and (3) measurements of cellular stress pathways in breast and ovarian cancer.

Read More about Jeffrey Brodsky
Serah Choi

Serah Choi

Program: Genome Stability

chois8@upmc.edu 5230 Centre Ave
Pittsburgh PA
Summary

I am a radiation oncologist whose clinical interest is in advancing care for patients with central nervous system tumors. My laboratory research is specifically on targeting a glucose transporter as a radiosensitizer for brain tumors.

Read More about Serah Choi
Yuanpu Di

Yuanpu Di

Program: Genome Stability

412-624-8718 peterdi@pitt.edu GSPH-4139
130 DeSoto Street
Pittsburgh PA
Summary

The purpose of my laboratory’s research is to investigate the effects of environmental exposure on the host. We are particularly interested in infection and immunity on the lung and its associated pathophysiological response during injury, repair, and regeneration. The primary focus of my current research is the cellular and molecular actions of exposures to toxic chemicals and microorganisms that underlie the pathogenesis of chronic human diseases. Areas of research: 1. Lung epithelial cell phenotype, differentiation, and function upon exposure; 2. Inflammation-associated tissue remodeling and lung tumorigenesis; 3. Development of novel antibiotics to overcome antimicrobial resistance (AMR).

Read More about Yuanpu Di
Wei Du

Wei Du

Program: Genome Stability

(412) 623-2211 wed41@pitt.edu 5117 Centre Ave
Suite G.5c
Pittsburgh PA
Summary

Dr. Du's research is centered on pathophysiology of hematologic diseases such as bone marrow (BM) failure and leukemia. She has a broad background in hematopoiesis, stem cell biology & aging, cellular metabolism and tumor microenvironment, with specific training and expertise in DNA damage response/repair, metabolite profiling, and in vivo disease modeling. Her early research covered understanding the mechanism of hematopoietic stem cell (HSC) mobilization and BM niche engraftment as well as the factors implicated in cell proliferation and apoptosis; identification of functional interactions between certain factors implicated in cell polarity, adhesion/migration, stem cell metabolism and aging. Her current research interests include: 1) Define the molecular and functional collaboration between a major cell signaling (FA) pathway and immunometabolic regulation in HSCs; 2) Target stem cell-niche interaction for improved therapy for patients with bone marrow failure and leukemia; 3) Study a novel interplay between DDR and immune responses in FA leukemogenesis; 4) Study on the systemic immune effects of persistent DNA damage using mouse and human models of DNA repair deficiency and aging; and 5) Mechanistic and functional elucidation of the role of a novel paracrine Wnt5a-Prox1 signaling axis in regulating HSC regeneration under conditions of injury and aging.

Read More about Wei Du
Andrew Duncan

Andrew Duncan

Program: Genome Stability

Summary

Research in the Duncan Lab focuses on liver development, homeostasis, and regeneration. Polyploidy is a defining feature of the adult liver. Hepatocytes are either mononucleated or binucleated, and ploidy is determined by the number of nuclei per cell as well as the ploidy of each nucleus. Although hepatic polyploidy has been described for well over 100 years, the functional role of hepatic polyploidization is unclear. Dr. Duncan’s lab recently showed that regenerating polyploid hepatocytes undergo specialized cell divisions to form aneuploid daughter cells, generating a high degree of genetic diversity within the liver. Moreover, in rodent models, chromosome-specific aneuploid hepatocytes were shown to play a specialized role in liver regeneration, promoting adaptation and resistance to different forms of chronic liver injury. 

Read More about Andrew Duncan
Elise Fouquerel

Elise Fouquerel

Program: Genome Stability

(412) 623-3237 fouquerele3@upmc.edu Hillman Cancer Center Suite 2.26f
5115 Centre Ave
Pittsburgh PA
Summary

The overarching goal of my research is to understand the cellular mechanisms that lead to genome instability, focusing on regions of the genome especially vulnerable to harmful environmental exposures. I particularly focus on defining the roles of ADP-Ribose transferase enzymes (ARTs/PARPs) in orchestrating the maintenance of both telomere and centromere integrity when exposed to chronic oxidative stress, a leading cause of tumorigenesis. DNA-dependent PARPs are key components of the DNA damage response and as such, are primary targets in cancer therapies. However, little is known on how PARPs operate at telomeres and centromeres upon oxidative DNA damage induction and how PARP inhibitors affect non-diseased cells in cancer patients. My laboratory’s mission is to therefore develop a research program that will provide a deep mechanistic understanding of genotoxic stress-dependent cancer development and inform the rational design of cancer treatments which will ultimately reveal fruitful in a translational and clinical setting to provide therapeutic alternatives. Beside support from the UPMC Hillman Cancer Center start-up funds, my laboratory is currently funded by (i) an R00 (NCE; NIEHS) to investigate the roles of PARP1 and PARP2 in the repair of oxidative DNA damage and the resolution of G quadruplex structures at telomeres as well their role in regulating telomerase enzyme; and (ii) an MIRA R35 (NIGMS) that investigates the impact of oxidative stress on centromere integrity and cell viability as well the specific roles of PARP enzymes in preserving their integrity. Pending R01 grant proposes to investigate R-loop structures as novel substrates for PARP1 and focuses on uncovering PARP1 function in their resolution.

Read More about Elise Fouquerel
Deborah Galson

Deborah Galson

Program: Genome Stability

412-623-7735 galson@pitt.edu Hillman Cancer Center Suite 1.19b
5117 Centre Avenue
Pittsburgh PA
Summary

Dr. Deborah Galson's laboratory is focused on two main areas:

(1) Determining the mechanism by which multiple myeloma (MM) cells reduce bone formation via suppression of the differentiation capacity of osteoblast progenitor cells in a manner that persists even after removal of the myeloma cells. These MM-altered bone marrow stromal cells also enhance osteoclastogenesis and microenvironmental support of myeloma growth. We have shown that myeloma cells induce the upregulation of expression of the transcriptional repressor Gfi1 in osteoblast precursor cells and that Gfi1 has a role in repressing Runx2, the key osteoblast transcription factor. We are currently investigating the mechanisms by which Gfi1 represses Runx2; MM cells and TNF-alpha/IL-7 regulate Gfi1 expression and activity; and roles for Gfi1 in MM cells and osteoclasts. Our preliminary data suggests that Gfi1 may prove to be a useful 3-way therapeutic target in MM bone disease. We are also expanding these studies into other cancer-induced bone disease models and into inflammatory diseases that cause bone formation suppression.

(2) Determining the mechanism by which measles virus nucleocapsid protein (MVNP) activates cellular genes and alters osteoclast differentiation. MVNP has been shown to be able to induce a Pagetic phenotype when transduced into osteoclast precursors and there is increasing evidence that it can play a role in the development of Paget's disease. Understanding the mechanisms involved may aid in developing additional treatments for Paget's disease as well as increase our understanding of how viral proteins alter cells. We have made the important discovery that MVNP signals through the IKK family members TBK1 and IKKepsilon to increase IL-6, a key player in creating the pagetic microenvironment. We are also studying MVNP regulation of C/EBPbeta and FoxO proteins, as well as autophagy, in generating aberrant osteoclasts. We have found that MVNP alters both the level of C/EBPbeta expression as well as the translation regulation of the C/EBPbeta LAP/LIP isoforms ratio. MVNP also alters the regulation of FoxO1 cellular localization, preventing nuclear localization, which increases autophagy, Further, MVNP alters the stability of FoxO3a, leading to rapid degradation and loss of SIRT1 expression, which thereby increases NF-kappaB activity. We are expanding the investigation of TBK1 and IKKepsilon signal transduction into other disease models that elevate osteoclasts including cancer-induced bone disease and arthritis.

Research Interests and Keywords
  • bone biology
  • Breast Cancer
  • cancer-induced bone disease
  • epigenetic regulation
  • Multiple Myeloma
  • Paget's disease
  • Signal Transduction
  • Transcription Factors
Read More about Deborah Galson
Joel Greenberger

Joel Greenberger

Program: Genome Stability

412-647-3602 greenbergerjs@upmc.edu UPMC Shadyside Radiation Oncology
UPMC Cancer Pavilion, POB2, Rm. 533 5150 Centre Avenue
Pittsburgh PA
Summary

Dr. Greenberger is examining the use of manganese superoxide dismutase (MnSOD) plasmid liposome gene therapy and GS-nitroxides, and other new second generation probiotics LR-IL22 and LR-IFN-B as agents to protect the normal tissues in the esophagus and lung from damage during radiation therapy. Damage to normal tissues during radiation therapy has been a major limitation to the effective treatment of lung cancer. The goal of his research is to improve the quality of life for cancer patients by potentially allowing the use of higher doses of radiation or chemotherapy to effectively treat lung cancer without the damaging side effects.

Research Interests and Keywords
  • Lung Cancer
  • Radiation mitigator
  • Radiation Protection
Read More about Joel Greenberger
Aditi Gurkar

Aditi Gurkar

Program: Genome Stability

Read More about Aditi Gurkar
Valerian Kagan

Valerian Kagan

Program: Genome Stability

kagan@pitt.edu 333 CLMCS
100 Technology Drive
Pittsburgh PA
Summary

Dr. Valerian E. Kagan is one of the world’s recognized leaders and one of the most prominent authorities in the field of Free Radical Biology and Medicine. Internationally known for his profound interdisciplinary studies of oxidative stress, antioxidants, tissue, and cell acute and chronic injury, he has founded a new field of research “Oxidative Lipidomics” and demonstrated its research power in investigations of cell death mechanisms. Free radicals, lipid peroxidation and oxidative stress have been long associated with tissue and cell damage through yet not well characterized specific mechanisms. The incompleteness of this knowledge is a stumbling block in discovery, development and effective implementation of antioxidant preventive and therapeutic strategies. The research performed by Dr. Kagan is a breakthrough in the field as it uncovers specific pathways through which enzymes of oxidative metabolism participate in the production of specific oxygenated lipid molecules that act as signals triggering cell death program as well as mechanisms involved in clearance of damaged or dead cells. Understanding these key signaling pathways is of prime importance for obtaining new insights into mechanisms of radiation injury, inflammation, and immune responses. Based on the discoveries of Dr. Kagan’s lab mechanism-based approaches to creation of novel generations of preventive, protective and mitigating small molecule drugs have been developed that are being tested in a number of conditions.

Research Interests and Keywords
  • antioxidant activity of pulmonary epithelial and endothelial proteins
  • Free radical biochemistry
  • nitric oxide (NO) interactions with cellular components
  • phospholipid signaling in cell death pathways
Read More about Valerian Kagan
Shihui Liu

Shihui Liu

Program: Genome Stability

Summary

The Liu Lab studies several medically important bacterial virulence factors, including anthrax toxins, in bacterial pathogenesis. Through investigating the interactions of these protein toxins and their mammalian hosts, we are interested in discovering the toxins’ molecular targets and understanding the molecular mechanisms of pathophysiology. We study how these toxins alter key signal transduction pathways, in particular the RAS and ERK pathways, in cancer cells and tumor stromal cells, and we use the knowledge obtained to design and develop novel bacterial toxin-based anti-tumor drugs with high tumor specificity. We are also interested in using this approach to design and develop novel biological-based therapeutics to selectively eliminate senescent cells. 

Read More about Shihui Liu
Silvia Liu

Silvia Liu

Program: Genome Stability

Read More about Silvia Liu
Songjian Lu

Songjian Lu

Program: Genome Stability

Summary

  • Using computational method to search for driver somatic genome alterations, such as somatic mutations, copy number alterations, that are related to cancer development.
  • Formulating the biological problems into graph or statistical problems.
  • Designing efficient exact algorithms for the hard computational problems.

Read More about Songjian Lu
Jianhua Luo

Jianhua Luo

Program: Genome Stability

412-648-8791 luoj@upmc.edu S-760 Scaife Hall
3550 Terrace Street
Pittsburgh PA
Summary

Dr. Luo's research is in the area of genome and gene expression studies of malignancies, especially in understanding how liver and prostate cancers obtain invasive and metastatic capabilities. Dr. Luo's laboratory in the past has primarily focused on the isolation and characterization of genes which are inactivated in liver and prostate cancers. His laboratory is currently focusing on characterizing oncogenic fusion genes in human malignancies and developing fusion gene targeting tools to diagnose and treat human cancers. Dr. Luo is also interested in developing long-read sequencing techniques to characterize isoform switches and mutation isoform expressions in human cancers.

Research Interests and Keywords
  • Biomarkers
  • Gene Expression
  • Genomics
  • Molecular Diagnostics
  • Prostate cancer
  • Signal Transduction
Read More about Jianhua Luo
Tatiana Moiseeva

Tatiana Moiseeva

Program: Genome Stability

(412) 864-7948 tatiana.moiseeva@pitt.edu UPMC Hillman Cancer Center, office 2.6a
5117 Centre Ave
Pittsburgh PA
Summary

DNA replication remains one of the main targets of cancer therapies as cancer cell generally proliferate faster and are prone to replication stress. My research interests involve studying the control of the initiation of DNA replication under normal conditions, in cancer, and in response to DNA damage. During my postdoctoral work, I have identified the signaling mechanism that mediates rapid and massive dormant origin firing in response to ATR or WEE1 inhibition. As a PI, I use ATR inhibition-induced origin firing, auxin-inducible degron systems, split Turbo-ID proteomics and other innovative cell biology approaches to study the molecular mechanism of the initiation of DNA replication in human cells. Our recent findings include discovery of the non-catalytic function of DNA polymerase epsilon and its dispensability for the assembly of CMG helicase in human cancer cells. My current projects focus on further studies into the non-catalytic function of DNA polymerase epsilon in cancer and non-cancer cells, identification of novel replication initiation factors in human cell lines, and the perturbations in replication proteins in cancers. Knowing the molecular mechanisms of origin firing will lead to developing drugs that specifically manipulate this process making cancer cells susceptible to DNA damage and other therapies. 

Read More about Tatiana Moiseeva
Yvonne Mowery

Yvonne Mowery

Program: Genome Stability

(412) 623-7088 yvm3@pitt.edu 5117 Centre Ave
Suite 2.26D
Pittsburgh PA
Summary

I am a physician scientist specializing in radiation therapy for the treatment of head and neck cancer and cutaneous malignancies. My laboratory utilizes genetically engineered mouse models, orthotopic syngeneic transplant mouse models, and patient samples to study the development and progression of head and neck squamous cell carcinoma (HNSCC), as well as to evaluate biomarkers and new therapeutic combinations for head and neck cancer. We are particularly interested in molecular characteristics of radiation resistance and immune dysregulation within the tumor microenvironment of HNSCC. 

Read More about Yvonne Mowery
Amitava Mukherjee

Amitava Mukherjee

Program: Genome Stability

(412) 623-3214 amitava.mukherjee@chp.edu Hillman Cancer Center
5115 Centre Ave
Pittsburgh PA
Summary

As a faculty in the Department of Radiation Oncology, I have been working on multiple cancer-related projects, including: 1. Using radiation as a modality in ovarian cancer mouse models in the presence of mitigators of radiation damage; 2. Ameliorating fibrosis in post-irradiated surviving lung cancer patients; 3. Evaluating senescence as an important factor in lung cancer progression. 

Read More about Amitava Mukherjee
Benjamin Nacev

Benjamin Nacev

Program: Genome Stability

412-623-7765 nacevba@upmc.edu Hillman Cancer Center Research Pavilion
5117 Centre Ave, Rm 2.6b
Pittsburgh PA
Summary

My long-term goal is to understand how perturbation of chromatin regulators disrupts the epigenome to affect fundamental epigenetically controlled processes. To address this question, I study genetic alterations in chromatin regulators that occur in sarcomas and other solid tumors. By combining my experience in pharmacology, genetics, chromatin biology, and sarcoma medical oncology, I am focused on addressing three major questions: 1) What are the effects of newly recognized cancer-associated histone mutations? 2) How do sarcoma-associated genetic alterations in chromatin regulators affect chromatin organization and function? 3) How might these alterations be targeted therapeutically?

In addition, I care for adult patients with sarcoma as a medical oncologist. I strive to encourage collaboration between my clinical and basic science colleagues by bringing my knowledge of both spheres into my work with others. Within my own group's, my goal is to develop projects that ultimately allow us to translate our laboratory discoveries back to the clinic to help patients.

Read More about Benjamin Nacev
Yael Nechemia-Arbely

Yael Nechemia-Arbely

Program: Genome Stability

Summary

CENP-A is a heritable epigenetic mark that determines centromere identity and is essential for centromere function. Centromeres are the central genetic element responsible for accurate chromosome segregation during cell division, and as such, they are anticipated to be evolutionarily stable. How centromeres evolved to allow faithful chromosome inheritance on an evolutionary timescale despite their epigenetic maintenance is unclear. One of our interests is understanding whether CENP-A is capable of precisely and stably specifying human centromere position throughout cellular proliferation. To investigate the positional stability of human centromeres as cells proliferate, we use a fibroblast cell line that harbors a neocentromere (epigenetic stable acquisition of a new centromere at a new chromosomal site).

Studying human centromeres epigenomics is challenging since human centromeres are found at unique DNA sequences, termed a-satellite, that is highly repetitive. Another research interest of our lab is tackling this challenging DNA and the histones and proteins bound to it, by using novel epigenomics tool such as DiMelo-seq that is a long-read, single-molecule method for mapping protein–DNA interactions genome wide. This method is essentially ChIP-seq on long-reads DNA sequences that can be sequenced using Oxford nanopore long-read sequencing. We are excited to determine the centromeric DNA sequences associated with different centromeric proteins across the cell cycle and how these may change when centromeric proteins are highly expressed, as seen in cancer, using this method.

CENP-A is highly expressed in several cancers, serving as a marker of poor prognosis. When overexpressed, CENP-A is ectopically loaded onto non-centromeric transcriptionally active sites. Ectopic CENP-A sites are removed during DNA replication to restrict CENP-A to the centromeres only, ensuring faithful chromosome segregation during mitosis and maintenance of genome stability. Induced overexpression of CENP-A in cancerous cells has been shown to lead to chromosome segregation defects and micronuclei formation. Whether the sole overexpression of CENP-A in non-transformed near-diploid cells can induce genomic instability that can drive tumor formation remain poorly understood and is another focus of our lab research.

Read More about Yael Nechemia-Arbely
Carola Neumann

Carola Neumann

Program: Genome Stability

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

The main interest of the Neumann laboratory is to expand our knowledge of cell signaling that is in part mediated by oxidation and reducing (redox) reactions as reactive oxygen species (ROS) deregulate the redox homeostasis and promote tumor formation by initiating an aberrant induction of signaling networks that cause tumorigenesis, including breast cancer. To investigate the specific mechanisms underlying redox-induced tumorigenesis, the Neumann laboratory focuses on the redox-induced posttranslational modifications (PTM) of protein cysteines, which are essential in cell signaling. Peroxiredoxin 1 (PRDX1) is a peroxidase that has emerged as a critical protein in cell signaling as it scavenges the second messenger H2O2, binds to and regulates signaling proteins, and when knocked out in mice, causes a variety of cancers, including breast cancer. 

Using this system, we have identified protein cysteines modified by ROS, contributing to breast cancer initiation and progression. For example, we have discovered that a previously unknown functionally essential cysteine in the recombinase RAD51 is vital for its function in homologous recombination-mediated DNA repair. Based on these findings, we have developed a reversible, non-toxic covalent inhibitor that targets this functionally essential RAD51 cysteine, thus inhibiting RAD51 function and, significantly, sensitizing triple-negative breast cancer cells to DNA-damaging therapies. Current work in the laboratory is geared towards successfully  IND-labeling the inhibitor and further discovering other functional protein cysteine targets that can be exploited as anti-cancer therapies.

Research Interests and Keywords
  • Breast Cancer
  • cell signaling
  • peroxiredoxin
Read More about Carola Neumann
Yuri Nikiforov

Yuri Nikiforov

Program: Genome Stability

412-864-6162 nikiforovye@upmc.edu 3477 Euler Way
Clinical Lab Building, 8th Floor Room 8031
Pittsburgh PA
Summary

Dr. Nikiforov's research is focused on thyroid cancer genomics and mechanisms of chromosomal rearrangements and other mutations induced by ionizing radiation in thyroid cells and other cell types. Since 2000, Dr. Nikiforov's research activities have led to four scientific discoveries. These discoveries described below have resulted in more than 120 published papers and form the basis of Dr. Nikiforov's current work. 1.The discovery that genes involved in recurrent chromosomal rearrangements in cancer cells are localized in proximity to each other in the nuclei of normal human cells at the time of exposure to ionizing radiation or other genotoxic stress (Science, 2000, 290:138-141). 2.The discovery that BRAF oncogene can be activated as a result of chromosomal rearrangement (J Clin Invest, 2005,115:94-101). 3.The discovery that in thyroid cancer, chromosomal rearrangements represent the main mutational mechanism in tumors arising as a result of exposure to ionizing radiation, whereas point mutations are a mechanism of spontaneous (chemical) carcinogenesis (J Clin Invest, 2005,115:94-101). 4.The discovery of ALK activation in thyroid cancer as a result of STRN-ALK fusion (PNAS, 2014, 111:4233-8). Current research activities of Dr. Nikiforov's lab are focused on further understanding the molecular mechanisms of radiation-induced carcinogenesis and chromosomal rearrangements in human cells. Specifically, the studies aim to establish the number of double-strand DNA breaks required for the formation of a chromosomal rearrangement after exposure to ionizing radiation and identify the DNA repair mechanisms involved in this process. The results of this research will allow better understanding of carcinogenesis induced by ionizing radiation and help to develop measures for alleviating and preventing the carcinogenic effect of radiation exposure. Another direction of Dr. Nikiforov's research is centered on finding novel mutations and gene fusions in thyroid cancer using next-generation sequencing and applying the current knowledge in molecular genetics of thyroid cancer to the clinical management of patients with thyroid nodules. Specifically, the studies in progress aim to define the diagnostic utility of molecular markers for preoperative diagnosis of cancer in thyroid fine-needle aspiration (FNA) biopsies and to characterize several novel chromosomal rearrangements discovered in thyroid cancer by next generation sequencing.

Research Interests and Keywords
  • chromosomal rearrangements
  • next-generation sequencing
  • novel mutations in thyroid cancer
  • radiation-induced carcinogenesis
  • Thyroid cancer genetics
  • thyroid fine-needle aspiration (FNA)
Read More about Yuri Nikiforov
Roderick O'Sullivan

Roderick O'Sullivan

Program: Genome Stability

osullivanr@upmc.edu Hillman Cancer Center
5117 Centre Avenue Suite 2.6d
Pittsburgh PA
Summary

The O’Sullivan lab at UPMC Hillman Cancer Center conducts research into proteins that alter the structural and epigenetic functions of human telomeres. Telomeres are structures at the ends of chromosomes – the integrity of telomeres is an important factor in maintaining genome stability to prevent cancer and accelerated aging. Current efforts in the lab relate to: (i) deciphering the relationship between the regulation between chromatin structure and telomere function and (ii) new aspects of ADP-ribosylation in genome stability.

Research Interests and Keywords
  • ADP-ribosylation
  • Cancer
  • DNA Damage
  • Epigenetics
  • Telomere
Read More about Roderick O'Sullivan
Patricia Opresko

Patricia Opresko

Program: Genome Stability

412-623-7764 plo4@pitt.edu UPMC Hillman Cancer Center Research Pavilion
5117 Centre Avenue, Suite 2.6a
Pittsburgh PA
Summary

My lab studies DNA damage and repair at telomeres. Telomeres are the caps at chromosome ends that are essential for preserving the genome. When chromosomes lose their telomere caps the cells age and this contributes to the onset of degenerative diseases with aging. If chromosomes lose their telomere caps in pre-cancerous cells, then this causes genetic alterations that hasten the progression to cancer. Understanding mechanisms of telomere damage and repair should lead to new intervention strategies aimed at preserving these regions of the genome that are so critical for protecting our chromosomes and maintaining youthful cells. Conversely, we aim to leverage new findings to develop therapeutic strategies that deplete telomeres in cancer cells to prevent them from dividing. 

Read More about Patricia Opresko
Anthony Schwacha

Anthony Schwacha

Program: Genome Stability

Read More about Anthony Schwacha
Saad Sheikh

Saad Sheikh

Program: Genome Stability

(412) 514-8534 sheikhs2@upmc.edu UPMC Hillman Cancer Center
5117 Centre Avenue, Suite 2.32f
Pittsburgh PA
Summary

The Sheikh lab is interested in understanding how various oncogenic drivers impact the response to DNA damage agents in pediatric CNS malignancies. Furthermore, we seek to determine how the alterations in the metabolome of pediatric CNS malignancies impact the response to DNA damage agents. Our ultimate goal is identify novel synergistic therapies that enhance the cell death response of pediatric brain tumors to DNA damage. 

Read More about Saad Sheikh
Heath Skinner

Heath Skinner

Program: Genome Stability

412-623-3275 skinnerh@upmc.edu UPMC Hillman Cancer Center, Research Pavilion
Suite 2.6a, 5117 Centre Ave.
Pittsburgh PA
Summary

Heath D. Skinner, MD, PhD, is a Professor in as well as the Chair of the Department of Radiation Oncology at the University of Pittsburgh and UPMC Hillman Cancer Center. In addition to his leadership and clinical duties, Dr. Skinner maintains an active, translational research laboratory focused upon identifying novel, clinically targetable biomarkers of resistance to radiation. His group utilizes "big data" approaches to clinical specimens as well as in vivo screening techniques to generate novel targets for study. These targets are then further investigated in vitro, to elicit insights regarding mechanisms of radioresistance. Dr. Skinner's research is designed to generate insights that led to the rational design of clinical trials using agents that are currently under investigation to minimize the time from bench to bedside. In addition to several current R01 grants, he is PI (along with Dr. Robert Ferris) of the UPMC Hillman Cancer Center Head and Neck SPORE. 

Research Interests and Keywords
  • DNA Damage
  • head and neck
  • HPV
  • p16
  • Radiation
Read More about Heath Skinner
Claudette St. Croix

Claudette St. Croix

Program: Genome Stability

Summary

Dr. St. Croix is a tenured Professor of Cell Biology and an Associate Director of the CBI. She has been a PI or co-I on NIH-funded R01s, P01s and R21s, and has been continuously funded by the NIH since 2005.  A major focus of the St. Croix laboratory is the use of advanced optical imaging technologies to dissect molecular signaling pathways controlling vascular function in rodent and zebrafish model systems of disease. Within the CBI, Dr. St Croix manages and directs the use and application of fluorescence-based optical microscopy with an emphasis on advanced tools multiparametric live cell microscopy, focused light intravital small animal imaging, super-resolution microscopy methods and complex image processing.

Research Interests and Keywords
  • Cell Biology
  • Image Analysis
  • Optical Microscopy
Read More about Claudette St. Croix
Donna Stolz

Donna Stolz

Program: Genome Stability

412-383-7283 dstolz@pitt.edu S221 BST-South
Pittsburgh PA
Summary

Dr. Donna Beer Stolz is the Associate Director of the Center for Biologic Imaging, University of Pittsburgh School of Medicine, and Professor in the Departments of Cell Biology and Pathology at the University of Pittsburgh. She has been the director of the Electron Microscopy arm if the CBI since 1997. Prior to arriving at the university, Dr. Stolz received her BS in Biochemistry in 1986 and a PhD in Molecular and Cellular Biology in 1991 from the University of Massachusetts, Amherst.

Dr. Stolz is the author/coauthor of over 370 publications from her work at the Center for Biologic Imaging as well as from her own research efforts. Her primary interests lie in coordinating imaging studies with investigators using transmission and scanning electron microscopy approaches and integrating a wide variety of optical and electron imaging technologies in cell biology. She is actively involved in medical and graduate student teaching.

Some of Dr. Stolz’s cancer-related outreach activities include:

  • HeLa Reflected Art Show (2011-2012): Curated HeLa cell-centric image art show for the 60th Anniversary of HeLa, Henrietta Lacks Memorial Lecture Series, Johns Hopkins Medical School, Johns Hopkins Institute for Clinical and Translational Research. 
  • Spring Flower Show, “The Secret Garden” (2013) and “Beneficial Insects” (2014): Curated photomicrographs of CBI and Pittsburgh’s Creative and Performing High School summer interns in Pittsburgh’s Phipps Conservatory lobby.
  • “One College One Community Reads” (2018) Community College of Allegheny County, Boyce Campus, Monroeville, PA. Keynote speaker and curated a 2-week art show of HeLa cell-related images to accompany the book by Rebecca Skloot, “The Immortal Life of Henrietta Lacks.”
     

Research Interests and Keywords
  • Electron Microscopy Technologies
  • Microscopy Outreach
  • Science as Art
  • Tissue and Cell Ultrastructure
Read More about Donna Stolz
Bennett Van Houten

Bennett Van Houten

Program: Genome Stability

vanhoutenb@upmc.edu Hillman Cancer Center
5117 Centre Avenue Lab 2.6e
Pittsburgh PA
Summary

Our laboratory studies the formation and repair of DNA damage in nuclear and mitochondrial genomes.  We are particularly interested in the structure and function of proteins that mediate DNA repair and the role of oxidative stress in human disease. We use state-of-the-art single molecule, biochemical and cell biology tools.

Research Interests and Keywords
  • Cancer pharmacology
  • DNA Repair
  • Drug Discovery
  • Single Molecule Analysis
Read More about Bennett Van Houten
Hong Wang

Hong Wang

Program: Genome Stability

how8@pitt.edu 130 De Soto Street
Pittsburgh PA
Summary

Dr. Wang’s primary areas of research interest include design and statistical analysis of clinical trials and pre-clinical studies, and correlated survival analysis. Other areas of interest include microbiome data analysis, statistical analysis of Multiplex Immunofluorescence (mIF) data, and in vitro and in vivo radiation survival analysis.

As a Research Associate Professor in the Department of Biostatistics, and Biostatistician and former Interim Director of UPMC Hillman Cancer Center (HCC) Biostatistics Facility, Dr. Wang has been collaborating with HCC medical investigators since 2004 by leading the statistical support of the Skin Cancer, Radiation Oncology, and Prostate/GU program. He has designed over 70 clinical trials. He has been working as a statistical reviewer for UPMC HCC PRC since 2006. He is the Co-Director of Biostatistics/Bioinformatics Core for Melanoma SPORE, and lead statistician for the NCI ETCTN trials Pittsburgh consortium. He has mentored 3 GSRs and advised 2 MS students.

Research Interests and Keywords
  • Clinical Trials
  • Microbiome Analysis
  • Multiplex Immunofluorescence (mIF) Analysis
  • Statistics in Cancer Biomarker Research
  • Survival Analysis
Read More about Hong Wang
Simon Watkins

Simon Watkins

Program: Genome Stability

swatkins@pitt.edu S225 BST-South
Pittsburgh PA
Summary

Optical Microscopy has formed the core of my research career since my graduate training in England.  In the CBI which I founded and direct, we build, test, and use cutting edge optical tools for all types of research microscopic imaging in cells, tissues and animals from the single molecule to the whole animal, the goal being to build highly flexible, maximally effective imaging solutions, to be used by academic researchers.  In fact a major focus of my career and of the Center is to develop, train and imbue researchers at all levels (undergraduate, student, post-doc and faculty) with a solid understanding (both theoretical and practical) of the power of microscopy.   As a professor of Cell Biology a major focus of my research has been to develop, build, and apply computer aided microscopes and analysis tools for imaging subcellular events at all levels of resolution within fixed and living systems. These include high speed Total internal Reflection Fluorescence microscopes able to image at 100 frames/second, high speed confocal systems able to collect multicolor 3D stacks in the second timeframe and other prototype confocal systems able to scan very large tissue sections with submicron resolution at very high speed. Most recently we have been developing very high speed deep tissue imaging solutions to collect quantitative images at the diffraction limit of entire tissues including brain, and building automated multi-spectral upright solutions combined with deep learning methods to dissect spectrally complex multiplex samples, including novel approaches for studying collagen organization in large tissue volumes. 

Research Interests and Keywords
  • cell imaging
  • Computer Aided Image Analysis
  • Image Processing
Read More about Simon Watkins

View Investigators by Last Name

A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z