Co-Leaders

Dario Vignali
Program: Cancer Immunology and Immunotherapy
Summary
Our research focuses on various aspects of T cell regulation and function:
(1) Mechanistic Focus:
(a) Immune Regulation: Regulatory T cells (Tregs): Identification of novel Treg molecules and their function; mechanism of Treg function; regulation of Treg stability via Nrp1 and other pathways; IL-35 signaling and mechanism of action; novel Ebi3 binding partner; IL-10 & IFNy function; neuron-immune interactions.
(b) Immune Regulation: Inhibitory Molecules: Identification of novel inhibitory receptors (IR) and their mechanisms; immune modulation of T cell subsets by LAG3; PD1 and NRP1; PD1-LAG3 synergy; mechanism of CD8+ and CD4_ T cell exhaustion; protein engineering to develop novel therapeutics.
(c) Structure-function analysis of T cell receptor (TCR):CD3 complex and LAG3 signaling: Mechanism of TCR:CD3 signaling; modulation & control of TCR signaling by IRs.
(d) Systems Immunology: Single cell systems approaches (transcriptomic & epigenomic) to hypothesis test, hypthesis generate and discover; technology and algorithm development; multispectral imaging.
(2) Disease Focus:
(a) Cancer: Biology of LAG3/PD1, IL-35 and NRP1 in mouse models of cancer and also in samples from treatment-naive patients or immunotherapy recipients; primary focus on solid tumors – head & neck, melanoma, lung, ovarian, breast cancer, with some work on pancreatic, GI and glioma cancers, and pediatric solid malignancies; novel approaches for therapeutic translation; biomarker discovery.
(b) Autoimmune and Inflammatory Disease: Impact, function & insufficiency of Tregs and IRs in several autoimmune and inflammatory disease with emphasis on models of autoimmune diabetes (NOD), EAE and asthma; development of therapeutic approaches (enhance Treg stability; IR agonists.
Research Interests and Keywords
- cytokine signaling,regulatory T cells,Tumor Immunology

Hassane Zarour
Program: Cancer Immunology and Immunotherapy
5117 Centre Avenue Lab 1.32a
Pittsburgh PA
Summary
Hassane Zarour, MD is a dermatologist and cancer immunologist whose research focuses on basic and translational human cancer immunology in the melanoma field. His work has led to the identification of novel melanoma MHC class II-presented epitopes that have been used in investigator-initiated trials at UPMC Hillman Cancer Center as well as in multi-center trials. Most recently, Dr. Zarour's work has contributed to elucidating the role of inhibitory receptors in promoting melanoma-induced T cell dysfunction in the tumor microenvironment. These findings led to the development of novel antibodies targeting inhibitory receptors for clinical trials. Dr. Zarour actively contributes to the design and the implementation of novel investigator-initiated trials based on laboratory findings, including two melanoma vaccine trials funded by the Cancer Research Institute and the National Cancer Institute, respectively. He is the lead scientific investigator on the Hillman Skin Cancer SPORE Project 3 that is testing the novel combination of BRAF inhibitor (BRAFi) therapy with high-dose interferon for metastatic V600E positive melanoma. He is also testing a novel combination of an anti-PD-1 antibody (MK 3475/Pembrolizumab) and PEG-interferon with grant support from an academic-industry award of the Melanoma Research Alliance.
Research Interests and Keywords
- cancer immunology,Cancer immunotherapy,Melanoma,skin cancer

Members

Oleg Akilov
Program: Cancer Immunology and Immunotherapy
Summary
Oleg E. Akilov, MD, PhD, is an Assistant Professor of the Department of Dermatology at the University of Pittsburgh and a Director of the Cutaneous Lymphoma Program and Extracorporeal Photopheresis Unit. Dr. Akilov directs Cutaneous Lymphoma Program providing the full spectrum of management of all stages of cutaneous lymphoma. He serves as a principal investigator on multiple clinical trials in cutaneous lymphoma. Additionally, Dr. Akilov is very enthusiastic about resident education and mentoring future dermatologists.


Robert Binder
Program: Cancer Immunology and Immunotherapy
200 Lothrop St.
Pittsburgh PA
Summary
Our research interests are focused on the mechanisms of cross-priming of antigens during immune responses to cancer, viruses and autoimmunity. The pursuit of this research area stems from the observations that in many situations, heat shock proteins (HSPs) are both necessary and sufficient for cross-presentation. HSPs are adept at this because of several unique properties, including their ability to:
- chaperone peptides;
- bind to HSP receptors (CD91) for endocytosis; and
- stimulate immune cells to up-regulate costimulation.
HSPs thus elicit remarkable immune responses specific for the peptides they chaperone. The laboratory is using these observations to examine new facets of antigen presentation and also to develop novel immunotherapies for cancer, infectious disease and autoimmune disorders.
A related area of research examines how other ligands for the HSP receptor CD91 interact with the immune system. In the past few years, we have shown that a2-macroglobulin (a2M), a CD91 ligand, though not a bonafide HSP, shares the immunogenic properties of HSPs and can elicit immune responses specific to (peptide) substrates that it chaperones. We are currently exploring the identification of naturally formed a2M-substrate complexes and the potential use of these immunogenic complexes as therapeutic agents for cancer and infectious disease.
Research Interests and Keywords
- Antigen cross-presentation
- Cancer Vaccines
- heat shock proteins
- Immunotherapy
- Tumor Immunology

Tullia Bruno
Program: Cancer Immunology and Immunotherapy
Summary
Immunotherapy, specifically anti-PD1, has improved patient survival in a range of tumor types including head and neck squamous cell carcinoma (HNSCC) and non-small cell lung cancer (NSCLC). Despite the success of anti-PD1 therapy, only 20% of patients produce a durable response to this treatment. Further, there are some solid tumor types i.e. ovarian cancer, which yield very little therapeutic benefit from current standard of care immunotherapies. Thus, a need exists to develop additional therapeutic strategies to treat these patients, which includes evaluation of other tumor infiltrating immune cells that could further augment the CD8+ and CD4+ intratumoral T cell response. B cells represent a possible target for immunotherapy due to their predominance in the tumor microenvironment (TME) and crucial role in the immune response. However, B cell function in cancer and in the context of immunotherapy has been understudied. In fact, conclusions on an anti- or pro- tumor role for B cells in the TME remain incomplete. However, in multiple solid tumors, current evidence suggests an anti-tumor role for B cells. Specifically, detection of B cells within tertiary lymphoid structures (TLS) correlates with increased survival and immunotherapeutic response. While B cells have been identified in multiple tumor types, their complete phenotypic signature and interplay with other components within the TME have been understudied. Further, the complex composition of TLS in patient tumors is severely underappreciated, which is an overt focus of the Bruno laboratory. Specifically, we aim to understand B cell infiltration and TLS development within solid tumors to generate effective B-cell focused immunotherapies to augment the current successes of standard of care immunotherapies such as anti-PD1.
To this end, we take a multi-level approach to understanding B cells and TLS composition in human tumors. Specifically, we transcriptionally assess B cells via single cell RNAseq with paired BCR seq, we interrogate B cell subsets within patient tumors using multi-parameter flow cytometry (15-30 parameters), we locationally evaluate B cells within and outside TLS utilizing multispectral imaging (Vectra Polaris) and spatial transcriptomics (Nanostring GeoMax Digital Spatial Profiler), and we evaluate the function of B cells and their interplay with other important immune cells within the TME via micro-scale in vitro functional assays.
Research Interests and Keywords
- B cells
- tertiary lymphoid structures
- Tumor Immunology



Diwakar Davar
Program: Cancer Immunology and Immunotherapy
5117 Centre Avenue
Pittsburgh PA
Summary
My research interests are in translational science. Specifically, I am interested in designing early-phase clinical trials based on an improved understanding of tumor immunobiology and host-tumor-microenvironment interactions. Additionally, I am interested in the mechanisms underlying non-response to checkpoint inhibition and novel approaches to overcome this non-response. My clinical interests are in the management of advanced melanoma and the development of early phase studies to test novel immunotherapeutic approaches singly and in combination in patients with advanced cancer.
Research Interests and Keywords
- checkpoint inhibition
- early phase clinical trials
- Immunotherapy
- Melanoma
- Tumor immunobiology
- Tumor Microenvironment

Greg Delgoffe
Program: Cancer Immunology and Immunotherapy
Summary
In recent years, the decades-long promise of tumor immunotherapy has finally begun to come to fruition. Checkpoint blockade, for example, represents a critically important intervention for potentiating the antitumor immune response. In these therapies, blockade of T cell intrinsic negative regulators (such as CTLA-4 and PD-1 signaling) releases the brake on effector T cells in the tumor, resulting in substantial, durable antitumor immunity, and clinical responses.
While negative regulators on the effector T cells can be relieved through these interventions, effector T cells still face a variety of cell extrinsic modes of immune suppression, notably through suppression via regulatory T (Treg) cells. Treg cells play critical roles in preventing autoimmune responses to self tissues as well as limiting immunopathology during exuberant immune responses. However, Treg cells represent a major barrier to antitumor immunity. Many tumors recruit, activate, and expand large numbers of Treg cells, which can be specific for any number of normal, self antigens expressed by the tumor. While depletion of total Treg cells can result in autoimmune pathologies, inhibition of Treg cell stability or function has been shown to allow for local inhibition of Treg cell suppression in the tumor, while sparing normal tissues from an autoimmune response.
Thus, finding phenotypic, signaling, or functional parameters that distinguish intratumoral Treg and conventional T (Tconv) cells could shed light on mechanisms by which Treg cells could be targeted to allow for a greater antitumor response. Recent studies have found that Tconv and Treg cells have distinct metabolic requirements. Not unlike cancer cells, conventional T cells undergo aerobic glycolysis (the 'Warburg effect') when undergoing robust expansion. However, regulatory T cells utilize alternative sources of fuel. Our initial findings in the laboratory suggest that not only do intratumoral Treg cells utilize distinct fuel from their conventional brethren, but engage different metabolic pathways from Treg cells in normal tissues and lymphoid organs. This suggests that metabolic pathways, or their downstream targets, could be targeted in order to inhibit intratumoral Treg cells specifically, releasing a crucial cell extrinsic brake on the antitumor immune response. The goal is to provide alternative modalities of therapy that could be utilized alone or in combination with other immunotherapeutic strategies, to allow for robust and durable immune responses for the eradication of cancer.
Research Interests and Keywords
- Cancer immunotherapy
- immunometabolism
- regulatory T cells
- Tumor Immunology

Rajeev Dhupar
Program: Cancer Immunology and Immunotherapy
Summary
I have been building a program around utilizing malignant pleural effusions as a source of immune cells and tumor cells for the study of cancer evolution as well as potential immunotherapeutics. I have collaborated with several investigators (Lotze, Bruno, Lee/Oesterreich, Donnenberg) and work closely with the immunologist Dr. Adam Soloff within my Department.

Albert Donnenberg
Program: Cancer Immunology and Immunotherapy
Suite 300
Pittsburgh PA
Research Interests and Keywords
- cancer stem-cell hypothesis
- Hematopoietic Stem Cell Transplantation
- technological advances in flow cytometry
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Robert Edwards
Program: Cancer Immunology and Immunotherapy
Summary
Dr. Edwards' research interests include cervical and ovarian malignancies. He serves as principle investigator of the Gynecologic Oncology Group for the University of Pittsburgh and for a number of pharmaceutical-sponsored studies. He also serves on the Cancer Vaccine Committee, which experiments with novel therapeutic approaches to gynecologic malignancies and produces translational research.
Three specific targets of Dr. Edwards' research include: 1) vaccine therapies for cervical and ovarian cancer; 2) combining biologic and immunologic therapies with traditional therapies in the treatment of women's cancer; and 3) intraperitoneal therapy.
Research Interests and Keywords
- cervical cancer
- Clinical Trials
- gynecologic malignancies
- Immunotherapy
- intraperitoneal chemotherapy
- ovarian cancer

Louis Falo
Program: Cancer Immunology and Immunotherapy
Summary
Dr. Falo is actively involved in a variety of research projects focused on the prevention and treatment of melanoma and skin cancers, and has research expertise in the areas of cutaneous drug delivery, radioprotection, immunobiology, vaccine design, antigen processing and presentation, dendritic cell biology, and molecular immunobiology and immunotherapy.
Research Interests and Keywords
- Cancer Vaccines
- Dendritic Cells
- Immunotherapy
- Melanoma
- skin cancer
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Robert Ferris
Program: Cancer Immunology and Immunotherapy
Cancer Pavilion, Suite 500 5150 Centre Ave.
Pittsburgh PA
Summary
Dr. Ferris's laboratory is focused on understanding basic immunological mechanisms of the T lymphocyte response to cancer, for the development of novel immunotherapeutic approaches to head and neck cancers (HNC). Tumor vaccine clinical trials are currently underway and new strategies are in development. We are particularly interested in the immune response to human papillomavirus (HPV)-associated head and neck cancer, which appears to be a distinct subgroup of head and neck squamous cell carcinomas. Monitoring the successful immune effects of individuals treated with immunotherapy is a major effort, in order to develop improved generations of vaccine approaches. We are also studying tumor induced immune evasion, such as defective antigen processing and presentation to subvert cytotoxic T lymphocyte recognition of tumors.
Another area of study involves the promotion of tumor metastasis by a family of molecules called chemokines. We are finding important roles for chemokine receptors in cancer metastasis. These chemokines are small, secreted molecules that mediate homing and recruitment of immune cells in response to inflammation, through a family of G-protein linked receptors. Overall, these studies are designed to identify the chemokines relevant to progression of HNC and to provide initial data on their possible clinical utility as components of future vaccination therapies for HNC. In addition, our group is interested in developing immune/inflammatory biomarkers present in the bloodstream for HNC detection, and monitoring in populations at risk for cancer recurrence and/or second primary tumors.
Research Interests and Keywords
- Antigen Presentation
- Cancer Vaccines
- CXC chemokines
- head and neck cancer
- HPV
- Immunotherapy
- Squamous cell carcinoma
- Tumor Microenvironment
- viruses and cancer
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Olivera Finn
Program: Cancer Immunology and Immunotherapy
Pittsburgh PA
Research Interests and Keywords
- Cancer Vaccines
- tumor-specific immunity




Reinhard Hinterleitner
Program: Cancer Immunology and Immunotherapy


Yen-Michael Hsu
Program: Cancer Immunology and Immunotherapy
Summary
1. Establishing novel experimental cell-based immunotherapies against human cancer. With my prior collaboration on developing an anti-ICAM1 CAR T against anaplastic thyroid cancer, I am interested in using and modifying the existing anti-ICAM CAR T (under FDA IND# 19291) as a novel therapy against multiple myeloma. Additionally, I am also interested in developing a mRNA CAR T program as a possible treatment modality against other malignancies under an industry sponsored research program.
2. Optimization of hematopoiesis and immune effector cells by vascular niche. My prior research efforts (Greenbaum A*, Hsu YM*, et al. Nature. 2013 *Equal contribution) have let to the discovery of tissue-specific niche factors that are critical for HSPC maintenance, expansion, and mobilization. In collaboration with Shahin Rafii at Weill Cornell Medicine, I am interested in investigating the effectiveness and the associated mechanism to expand human hematopoietic stem cells and and immune effector cells (e.g. cross-presenting dendritic cells) with modified human vascular niche.
3. Laboratory investigator for cell therapy based clinical trials at University of Pittsburgh and Hillman Cancer Center. As the Director of UPMC Hillman Cancer Center Immunologic Monitoring and Cellular Products Laboratory (IMCPL), I am interested in serving as a Co-investigator and laboratory lead in enabling many cell-based IND clinical trials at UPMC.


Alok Joglekar
Program: Cancer Immunology and Immunotherapy
Summary
The research in my laboratory focuses on using T cell antigen discovery techniques to understand and engineer immunity. One of the areas we are interested in is uncovering the targets of antitumor T cell responses and using this knowledge to engineer novel therapies.


Lawrence Kane
Program: Cancer Immunology and Immunotherapy
Summary
My lab is focused on the study of signal transduction pathways that regulate antigen-dependent activation of T cells and mast cells. Toward that end, we are engaged in several specific projects: 1. Understanding the signaling pathways downstream of Carma1, MALT1 and Bcl10 (CBM complex) in T cells 2. Defining biochemical and spatial regulation of NF-kB activation by the TCR/CD3 complex, along with CD28 co-stimulation 3. Understanding signal transduction pathways downstream of the transmembrane proteins Tim-1 and Tim-3, in T cells and mast cells
Research Interests and Keywords
- co-stimulation
- Immunology
- kinases
- Mast Cells
- Signal Transduction
- T cells

John Kirkwood
Program: Cancer Immunology and Immunotherapy
UPCI Research Pavilion 5117 Centre Avenue, Suite 1.32
Pittsburgh PA
Summary
The Kirkwood laboratory is engaged in the study of melanoma immunobiology, and the assessment of multiple new immunomodulators in the context of trials conducted by the Hillman Melanoma Program, and the SPORE in Melanoma and Skin Cancer, as well as the International Melanoma Working Group. The study of predictive and prognostic biomarkers of melanoma complements the studies of molecular inhibitors of melanoma signaling and immunomodulatory agents given alone and in combination with one another.
Research Interests and Keywords
- Cancer Vaccines
- Clinical Trials
- Immunology
- Immunotherapy
- Interferon
- Melanoma



Michael Lotze
Program: Cancer Immunology and Immunotherapy
Suite 300
Pittsburgh PA

Jason Luke
Program: Cancer Immunology and Immunotherapy
UPMC Cancer Pavilion, 5th floor, Room 563
Pittsburgh PA
Summary
I am Associate Professor of Medicine at the University of Pittsburgh Medical Center and Director of the Cancer Immunotherapeutics Center at Hillman Cancer Center who focuses on translational therapeutic advances for malignant melanoma and early phase drug development for advanced cancers. I have particular expertise in the immunotherapy of cancer, having been a lead investigator for immunotherapies such as anti-PD1/L1, CTLA4, LAG3, TIM3, GITR, OX40, CD137, CD40, inhibitors of indolamine-dioxygenase, adenosine A2a receptor & arginase as well as agonists of STING & oncolytic virus. I maintain an on-going interest in the molecular biology of cancer and particularly in the intersection between oncogene targeted small molecules and immunotherapy. I have pursued large scale biobanking efforts surrounding cancer immunotherapy and am interested in identifying tumor-intrinsic mechanisms of immune exclusion from patient samples by employing multi-omic bioinformatic approaches. I have been successful in obtaining independent support for clinical investigation from private, public and industry sources.

Haider Mahdi
Program: Cancer Immunology and Immunotherapy
Summary
Cancer related research: 1. Tumor immune microenvironment in ovarian cancer focusing on tumor associated macrophages and TGF-B as well as strategies to enhance benefit of immunotherapy in ovarian cancer; 2. Her2 directed targeted therapy in combination approach targeting resistance mechanisms; 3. DNA-damage response targeted therapy based on ATR targeted therapy in combination approach to reverse PARPi resistance in ovarian cancer.

Marcus Malek
Program: Cancer Immunology and Immunotherapy
One Children’s Hospital Drive, 4401 Penn Ave.
Pittsburgh PA


Yana Najjar
Program: Cancer Immunology and Immunotherapy
5117 Centre Avenue
Pittsburgh PA
Summary
I aim to advance the treatment of melanoma by complementing clinical care with the principles of translational science. Specifically, my research focuses on immunotherapy in advanced melanoma and its impact on the tumor microenvironment and the peripheral immune system. My goal is to develop rational combinations of immunotherapy, targeted therapy and other agents that may potentially remodel the tumor microenvironment in order to render it less hostile to the host immune system.

Abigail Overacre-Delgoffe
Program: Cancer Immunology and Immunotherapy
Summary
My broad research program will address the following question: How can the microbiome-specific immune response be modified or targeted to improve cancer patient response to immunotherapy? I will utilize the expertise and tools I have developed throughout my training to track and modify tumor- and microbiota-specific T cells in hopes of identifying current immunotherapeutic hurdles and developing targeting strategies for these unique cell populations. In addition, I will assess how previous therapies or other external changes to the gut microbiome impact response to immunotherapy in both mouse models and patient samples. Ultimately, I will define the interplay between the immune responses to the ever-changing gut microbiome during tumorigenesis. These studies have the potential to not only improve our understanding of resistance to immunotherapy in cancer, but also to identify novel means of enhancing anti-tumor responses through modulation of the microbiota or its products.
My previous work as a Damon Runyon postdoctoral fellow in the Hand lab focused on the study of bacteria-specific CD4+ T cells in colorectal cancer (CRC) after microbiome modulation with a single bacteria, Helicobacter hepaticus (Hhep). We found that bacteria-specific CD4+ T cells were sufficient to drive anti-tumor immunity and lead to an increase in organized tertiary lymphoid structures and tumor immune infiltration. Interestingly, tumor clearance was dependent on CD4+ T cells but not CD8+ T cells, the latter of which is the primary target population for most immunotherapies. These observations were published in Immunity (2021) and suggested for the first time that CD4+ T cells that are specific to the microbiome directly support the anti-tumor immune response and may represent a new therapeutic target in tumors that occur at barrier surfaces such as CRC. In addition, I have recently found that modulation of the colon microbiome through colonization with Hhep can have beneficial impacts on tumors located in distant barrier sites as well, such as the skin. I have combined a number of innovative tools and techniques with tumor lines that contain controlled and tunable neoantigens to track tumor- and bacteria-specific immune responses. I believe that these models will provide tremendous and unique tools that will aid my overarching research program of study.

Hyun Park
Program: Cancer Immunology and Immunotherapy
Summary
To identify molecular differences between responders and non-responders in cancer immunotherapies, we develop data-science techniques, AI-driven tools, and statistical inference methods. Based on the models, we attempt to stratify patients that will likely benefit from immunotherapies and identify potential therapeutic agents in collaboration with Drs. Hassane Zarour, Kathy Shair, and Masa Shuda.

Ravi Patel
Program: Cancer Immunology and Immunotherapy
Summary
I am a physician-scientist in the Department of Radiation Oncology here at Hillman. The focus of my translational research lab is on the development of new combination radiation immunotherapy treatments. In particular, my current research focus is on the development of targeted radiopharmaceutical therapies to enhance efficacy of immune checkpoint blockade in a variety of cancer models. I currently serve as an Authorized User for the In Vivo Imaging Core Facility and have developed several collaborations with investigators in Hillman. Moreover as a clinician, I treat GU, breast, and cutaneous malignancies and I am involved in translational clinical trials. As a member of the cancer center, I hope to foster collaborations within my clinical department in Radiation Oncology with the greater Hillman community for translational research.

Arjun Pennathur
Program: Cancer Immunology and Immunotherapy
3471 Fifth Avenue Suite 401.8
Pittsburgh PA

Amanda Poholek
Program: Cancer Immunology and Immunotherapy
Summary
My research is focused on understanding how tissue-specific signals control immune cell differentiation and function and the transcriptional and epigenetic level. To that end, I have been collaborating with Dr. Greg Delgoffe for over three years to understand the tumor-specific signals that control exhausted CD8 T cells and limit tumor clearance. This existing collaboration between my lab and the Delgoffe lab has already generated several publications as well as co-PI and co-I grant applications including several funded grants through the Mark Foundation for Cancer Research and the Cancer Research Institute.

Ian Pollack
Program: Cancer Immunology and Immunotherapy
Summary
Prior to joining the faculty of the Department of Neurological Surgery at the University of Pittsburgh in 1992, Dr. Ian Pollack was awarded the 1991 Van Wagenen Traveling Fellowship, which afforded him a year of subspecialty training in the Department of Neurosurgery at the Hospital for Sick Children in Toronto, the Neuro-Oncology Laboratory of the University of Lausanne in Switzerland, and the Laboratory of Tumor Biology of the University of Uppsala in Sweden. Dr. Pollack graduated magna cum laude from Emory University in 1980, where he earned a BS degree in chemistry. He received his medical degree from the Johns Hopkins University School of Medicine in 1984, then completed a surgical internship and neurosurgical residency at the University of Pittsburgh School of Medicine. Dr. Pollack has published more than 250 papers in refereed journals, numerous book chapters and invited papers, and has edited two books on childhood brain tumors. He is co-editor of the recently published book Principles and Practice of Pediatric Neurosurgery and an accompanying atlas Operative Techniques In Pediatric Neurosurgery. He is currently a principal investigator on numerous NIH grants focusing on novel therapies for brain tumors and evaluating molecular markers of tumor prognosis. He has co-chaired the National Cancer Institute Brain Malignancy Steering Committee since 2010.
Research Interests and Keywords
- brain tumor clinical trials
- brain tumor vaccines
- congenital spinal abnormalities
- craniofacial surgery
- Pediatric Neuro-oncology
- Pediatric neurosurgery

Mark Shlomchik
Program: Cancer Immunology and Immunotherapy
E1040 BSTWR
Pittsburgh PA
Research Interests and Keywords
- B cell development
- immunopathogenesis



Michael Shurin
Program: Cancer Immunology and Immunotherapy
Research Interests and Keywords
- Cancer immunotherapy
- Dendritic Cells
- psychoneuroendocrine factors of immunosuppression in cancer
- Tumor-induced immunomodulation

Adam Soloff
Program: Cancer Immunology and Immunotherapy
5117 Centre Avenue
Pittsburgh PA

Walter Storkus
Program: Cancer Immunology and Immunotherapy
Summary
Our laboratory research focuses on the study of tumor immunobiology and designing immunotherapies for the treatment of cancer. Our translational murine models and human in vitro studies are intended to serve as a foundation for the development of phase I/II clinical trials of modalities that can more effectively treat patients with melanoma or renal cell carcinoma. Such modalities include dendritic cell (DC)-based vaccines, cytokine gene-modified DC injected directly into tumor lesions, and combinational approaches integrating agents that modulate tumor cell immune recognition (i.e., HSP90 inhibitors) or alter the balance of Type-1 versus regulatory immunity in the tumor microenvironment (i.e., sunitinib). Most recently, we have discovered that immune targeting of the tumor-associated vasculature occurs naturally as a consequence of effective immunotherapy (via DC1-based cross-priming of T cells), and that vaccines based on tumor-associated blood antigens (TBVA) can promote tumor regression even in cases where cancer cells cannot be directly recognized by the protective CD8+ immune system. We have also determined that anti-angiogenic agents such as the tyrosine kinase inhibitors sunitinib, axitinib and dasatinib all lead to tumor vascular normalization and to the improved delivery of anti-TBVA T cells into the tumor microenvironment (TME) allowing for improved anti-tumor efficacy. This has most recently resulted in the development of our NIH-supported clinical trial UPCI 12-048 'A Randomized Phase II Pilot Study of Type I-Polarized Autologous Dendritic Cell Vaccines Incorporating Tumor Blood Vessel Antigen (TBVA)-Derived Peptides in Combination with Dasatinib in Patients with Metastatic Melanoma' (H. Tawbi, Clinical PI) that is currently accruing patients.
Research Interests and Keywords
- Cancer Vaccines
- Dendritic Cells
- Gene therapy
- Immunotherapy
- Melanoma
- Renal cell carcinoma
- Tumor biology

Dario Vignali
Program: Cancer Immunology and Immunotherapy
Summary
Our research focuses on various aspects of T cell regulation and function:
(1) Mechanistic Focus:
(a) Immune Regulation: Regulatory T cells (Tregs): Identification of novel Treg molecules and their function; mechanism of Treg function; regulation of Treg stability via Nrp1 and other pathways; IL-35 signaling and mechanism of action; novel Ebi3 binding partner; IL-10 & IFNy function; neuron-immune interactions.
(b) Immune Regulation: Inhibitory Molecules: Identification of novel inhibitory receptors (IR) and their mechanisms; immune modulation of T cell subsets by LAG3; PD1 and NRP1; PD1-LAG3 synergy; mechanism of CD8+ and CD4_ T cell exhaustion; protein engineering to develop novel therapeutics.
(c) Structure-function analysis of T cell receptor (TCR):CD3 complex and LAG3 signaling: Mechanism of TCR:CD3 signaling; modulation & control of TCR signaling by IRs.
(d) Systems Immunology: Single cell systems approaches (transcriptomic & epigenomic) to hypothesis test, hypthesis generate and discover; technology and algorithm development; multispectral imaging.
(2) Disease Focus:
(a) Cancer: Biology of LAG3/PD1, IL-35 and NRP1 in mouse models of cancer and also in samples from treatment-naive patients or immunotherapy recipients; primary focus on solid tumors – head & neck, melanoma, lung, ovarian, breast cancer, with some work on pancreatic, GI and glioma cancers, and pediatric solid malignancies; novel approaches for therapeutic translation; biomarker discovery.
(b) Autoimmune and Inflammatory Disease: Impact, function & insufficiency of Tregs and IRs in several autoimmune and inflammatory disease with emphasis on models of autoimmune diabetes (NOD), EAE and asthma; development of therapeutic approaches (enhance Treg stability; IR agonists.
Research Interests and Keywords
- cytokine signaling
- regulatory T cells
- Tumor Immunology

Anda Vlad
Program: Cancer Immunology and Immunotherapy
Summary
Proposing to identify immune biomarker discovery for disease management of endometriosis and ovarian cancer, the Vlad lab is investigating numerous questions about immune surveillance in women with these diseases. Via collaborations with our clinician colleagues at Magee-Womens Hospital of UPMC, the lab is working on implementing new clinical trials exploring the roles of novel immune biologics as adjuvant therapies in ovarian cancer.
Research Interests and Keywords
- Biomarkers
- Endometriosis
- immune surveillance
- Immunology
- ovarian cancer

Jing Wang
Program: Cancer Immunology and Immunotherapy
5117 Centre Avenue
Pittsburgh PA
Summary
The goals of my research program include: (1) define the cellular and molecular mechanisms of immune evasion during cancer development; (2) develop more effective cancer immunotherapy, with a focus on head and neck squamous cell carcinomas (HNSCCs) and B cell lymphomas; (3) elucidate the basic mechanisms of antibody gene diversification and B cell lymphomagenesis. We employ mouse models, human samples, and novel methodologies to elucidate mechanisms underlying the heterogeneous responses to immune checkpoint inhibitors in HNSCCs.

Theresa Whiteside
Program: Cancer Immunology and Immunotherapy
1.27d
Pittsburgh PA
Research Interests and Keywords
- Cancer immunotherapy
- Tumor Immunology


Hassane Zarour
Program: Cancer Immunology and Immunotherapy
5117 Centre Avenue Lab 1.32a
Pittsburgh PA
Summary
Hassane Zarour, MD is a dermatologist and cancer immunologist whose research focuses on basic and translational human cancer immunology in the melanoma field. His work has led to the identification of novel melanoma MHC class II-presented epitopes that have been used in investigator-initiated trials at UPMC Hillman Cancer Center as well as in multi-center trials. Most recently, Dr. Zarour's work has contributed to elucidating the role of inhibitory receptors in promoting melanoma-induced T cell dysfunction in the tumor microenvironment. These findings led to the development of novel antibodies targeting inhibitory receptors for clinical trials. Dr. Zarour actively contributes to the design and the implementation of novel investigator-initiated trials based on laboratory findings, including two melanoma vaccine trials funded by the Cancer Research Institute and the National Cancer Institute, respectively. He is the lead scientific investigator on the Hillman Skin Cancer SPORE Project 3 that is testing the novel combination of BRAF inhibitor (BRAFi) therapy with high-dose interferon for metastatic V600E positive melanoma. He is also testing a novel combination of an anti-PD-1 antibody (MK 3475/Pembrolizumab) and PEG-interferon with grant support from an academic-industry award of the Melanoma Research Alliance.
Research Interests and Keywords
- cancer immunology
- Cancer immunotherapy
- Melanoma
- skin cancer

Pascal Zinn
Program: Cancer Immunology and Immunotherapy
5150 Centre Ave., Suite 433
Pittsburgh PA
