Program Members

Co-Leaders

Leisha Emens, MD, PhD
Contact:
UPMC Hillman Cancer Center, Research Pavilion
Suite 1.46e, 5117 Centre Ave.
Pittsburgh PA
Phone: 412-623-3239
Dario Vignali, PhD
Contact:
99999
Pittsburgh PA
Research Interests and Keywords:
  • Regulatory T cells
  • tumor immunology
  • cytokine signaling
Hassane Zarour, MD
Contact:
Hillman Cancer Center, Research Pavilion
5117 Centre Avenue Lab 1.32a
Pittsburgh PA
Phone: 412-623-3244
Research Interests and Keywords:
  • Cancer immunology
  • cancer immunotherapy
  • melanoma
  • skin cancer
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.

Members

Carolyn Anderson, PhD
Program(s): Cancer Immunology and Immunotherapy
Contact:
100 Technology Drive
Bridgeside Point Suite 452
Pittsburgh PA
Research Interests and Keywords:
  • Radiopharmaceuticals
  • metal radionuclides
  • diagnostic imaging
  • cancer imaging
  • radiotherapy
  • molecular imaging
  • positron emission tomography (PET)
  • cancer metastasis
Summary
The major focus of the Anderson Lab is the development, evaluation and application of radiopharmaceuticals containing metal radionuclides for diagnostic imaging and radiotherapy. We are particularly interested in 64Cu (T1/2 = 12.7 hours), in large part because it emits beta+ particles for positron emission tomography (PET) imaging and beta- particles for targeted radiotherapy. We are also investigating 68Ga (T1/2 = 68 min) as a generator-produced positron-emitting radionuclide. The agents we are studying are 64Cu- and 68Ga-labeled chelator-peptide and monoclonal antibody conjugates for imaging and/or therapy of various types of cancer. One area of investigation in our laboratory is the development of radiolabeled alpha vs. beta 3 integrin ligands as PET agents for imaging bone metastasis. We have developed one agent, 64Cu-CB-TE2A-c(RGDyK), that specifically binds to alpha vs. beta 3 integrin in osteoclasts, which are bone resorbing cells that are present in high concentration in osteolytic bone lesions. This agent may be able to earlier detect painful, debilitating bone lesions associated with breast cancer, and multiple myeloma, as well as be used to determine early response to treatment of bone lesions associated with these diseases. Another area of focus for our lab is investigating imaging agents that target cell types, other than tumor cells, involved in cancer metastasis. For example, we are targeting integrin alpha 4 beta 1 as a marker of bone marrow derived cells that home to sites of metastasis prior to tumor cells as part of the pre-metastatic niche. We are also investigating immune cell types, such as macrophages, neutrophils and T-cells and their role in cancer and other diseases.
Maninjay Atianand
Program(s): Cancer Immunology and Immunotherapy
Kelly Bailey
Program(s): Cancer Immunology and Immunotherapy
David Bartlett, MD
Program(s): Cancer Immunology and Immunotherapy
Contact:
Hillman Cancer Center
5115 Centre Avenue 1.46 HCCLB
Pittsburgh PA
Phone: 412-623-7723
Research Interests and Keywords:
  • Tumor selective oncolytic vaccinia viruses
  • immunotherapy
  • regional cancer therapies
  • HIPEC
  • peritoneal surface malignancies
  • translational research
  • peritoneal mesothelioma
  • therapeutic cancer vaccines
Summary
Although my overall group is very active in a wide range of clinical trials and translational/clinical research, my specialty is in the regional delivery of chemotherapy to manage regionally confined, unresectable metastatic cancers, and my laboratory-based program is in the development of oncolytic viruses for regional therapy. I have developed tumor selective oncolytic vaccinia viruses that have been tested in pre-clinical models and clinical trials and have a successful history of transitioning benchtop findings into clinical trial applications.
Robert Binder, PhD
Program(s): Cancer Immunology and Immunotherapy
Contact:
E1051 BSTWR
200 Lothrop St.
Pittsburgh PA
Research Interests and Keywords:
  • Antigen cross-presentation
  • tumor immunology
  • immunotherapy
  • heat shock proteins
  • cancer vaccines
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:

  1. chaperone peptides;
  2. bind to HSP receptors (CD91) for endocytosis; and
  3. 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.

Lisa Borghesi, PhD
Program(s): Cancer Immunology and Immunotherapy
Contact:
Department of Immunology
Biomedical Science Tower, E1040 200 Lothrop St.
Pittsburgh PA
Phone: 412-383-7074
Research Interests and Keywords:
  • Stem cells
  • hematopoiesis
  • leukemia
  • transcription factors
  • TLRs
  • infection
  • inflammation
Summary
Dr. Borghesi's research focuses on hematopoietic stem cells (HSCs), the sole source of blood-forming cells throughout life. It has long been known that infection triggers dramatic and rapid changes in hematopoietic output, but the mechanisms remain murky. Toll-like receptor 4 (TLR4) is a dominant innate immune sensor for lipopolysaccharide (LPS) and hence a model receptor for how the hematopoietic system adapts to pathogen exposure. Dr. Borghesi's laboratory is studying the mechanisms that enable stem cells to directly sense infection, and functionally respond with accelerated differentiation and/or lineage fate re-direction. A second goal is to understand how disrupted patterns of differentiation give rise to cancers of the blood lineage. Dr. Borghesi's publications appear in the Journal of Experimental Medicine, PNAS, and Nature Immunology, and are frequently ranked by the Faculty of 1000.
Tullia Bruno, PhD
Program(s): Cancer Immunology and Immunotherapy
Contact:
Hillman Cancer Center, Suite 2.19
Pittsburgh PA
Phone: 412-623-2605
Yuri Bunimovich
Program(s): Cancer Immunology and Immunotherapy
Craig Byersdorfer
Program(s): Cancer Immunology and Immunotherapy
Contact:
Children's Hospital, Suite 5121
4401 Penn Avenue
Pittsburgh PA
Phone: 412-692-6664
Diwakar Davar, MD
Program(s): Cancer Immunology and Immunotherapy
Contact:
Hillman Cancer Center Research Pavilion, Suite 1.32d
5117 Centre Avenue
Pittsburgh PA
Phone: 412-623-7368
Research Interests and Keywords:
  • Tumor immunobiology
  • tumor microenvironment
  • checkpoint inhibition
  • early phase clinical trials
  • immunotherapy
  • melanoma
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.
Louise D'Cruze
Program(s): Cancer Immunology and Immunotherapy
Abbe de Vallejo, PhD
Program(s): Cancer Immunology and Immunotherapy
Contact:
4401 Penn Ave., Floor 9
Pittsburgh PA
Phone: 412-692-8455
Research Interests and Keywords:
  • T-lymphocytes
  • natural killer cells
  • immune remodeling
  • apoptosis
  • autoimmunity
  • inflammation
  • lymphocyte activation
  • transcription
Summary
Dr. de Vallejo's research program focuses on the immunobiology of inflammatory syndromes and aging. The long-term goal of his research is to unravel novel mechanisms of immune homeostasis that promote exceptional aging and longevity.
Greg Delgoffe, PhD
Program(s): Cancer Immunology and Immunotherapy
Contact:
Hillman Cancer Center, Suite 2.26e
5115 Centre Ave
Pittsburgh PA
Phone: 412-623-4658
Research Interests and Keywords:
  • Tumor immunology
  • regulatory T cells
  • immunometabolism
  • cancer 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.

Albert Donnenberg, PhD
Program(s): Cancer Immunology and Immunotherapy
Contact:
450 Technology Drive
Suite 300
Pittsburgh PA
Research Interests and Keywords:
  • Hematopoietic stem cell transplantation
  • bone marrow- and peripheral blood-derived stem and progenitor cells for regenerative therapy
  • cancer stem-cell hypothesis
  • technological advances in flow cytometry
Robert Edwards, MD
Program(s): Cancer Immunology and Immunotherapy
Contact:
204 Craft Avenue
Pittsburgh PA
Phone: 412-641-8556
Research Interests and Keywords:
  • Ovarian cancer
  • cervical cancer
  • gynecologic malignancies
  • intraperitoneal chemotherapy
  • immunotherapy
  • clinical trials
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.

Louis Falo, MD, PhD
Program(s): Cancer Immunology and Immunotherapy
Contact:
450 Technology Drive
Suite 300
Pittsburgh PA
Phone: 412-864-3760
Research Interests and Keywords:
  • Melanoma
  • skin cancer
  • immunotherapy
  • cancer vaccines
  • dendritic cells
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.
Robert Ferris, MD, PhD
Program(s): Cancer Immunology and Immunotherapy
Contact:
UPMC Hillman Cancer Center
Cancer Pavilion, Suite 500 5150 Centre Ave.
Pittsburgh PA
Research Interests and Keywords:
  • Antigen presentation
  • cancer vaccines
  • CXC chemokines
  • immunotherapy
  • squamous cell carcinoma
  • head and neck cancer
  • tumor microenvironment
  • viruses and cancer
  • HPV
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.

Olivera Finn, PhD
Program(s): Cancer Immunology and Immunotherapy
Contact:
E1044 BST (Office)
Pittsburgh PA
Research Interests and Keywords:
  • Cancer vaccines
  • tumor-specific immunity
Patrizia Fuschiotti, PhD
Program(s): Cancer Immunology and Immunotherapy
Contact:
W1052 BST
200 Lothrop St.
Pittsburgh PA
Research Interests and Keywords:
  • T cell differentiation
  • cytokines
  • immunology
Sarah Gaffen, PhD
Program(s): Cancer Immunology and Immunotherapy
Contact:
S702 BST South
Pittsburgh PA
Research Interests and Keywords:
  • IL-17-mediated signaling
  • oral mucosa
  • autoimmune disease
Yi-Nan Gong
Program(s): Cancer Immunology and Immunotherapy
Rachel Gottschalk
Program(s): Cancer Immunology and Immunotherapy
Timothy Hand
Program(s): Cancer Immunology and Immunotherapy
Reinhard Hinterleitner
Program(s): Cancer Immunology and Immunotherapy
Jing-Zhou Hou
Program(s): Cancer Immunology and Immunotherapy
Kabirul Islam, PhD
Program(s): Cancer Immunology and Immunotherapy
Contact:
1212 Chevron Science Center
219 Parkman Avenue
Pittsburgh PA
Research Interests and Keywords:
  • Epigenetics
  • small molecule therapeutics
  • chromatin-based proteomics and genomics
  • organic synthesis
Sawa Ito
Program(s): Cancer Immunology and Immunotherapy
Udai Kammula
Program(s): Cancer Immunology and Immunotherapy
Lawrence Kane, PhD
Program(s): Cancer Immunology and Immunotherapy
Contact:
E-1054 BSTWR
200 Lothrop St.
Pittsburgh PA
Phone: 412-383-6880
Research Interests and Keywords:
  • T cells
  • signal transduction
  • kinases
  • immunology
  • mast cells
  • co-stimulation
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
John Kirkwood, MD
Program(s): Cancer Immunology and Immunotherapy
Contact:
Hillman Cancer Center
UPCI Research Pavilion 5117 Centre Avenue, Suite 1.32
Pittsburgh PA
Phone: 412-623-3243
Research Interests and Keywords:
  • Melanoma
  • immunology
  • immunotherapy
  • interferon
  • cancer vaccines
  • clinical trials
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.

Gary Kohanbash
Program(s): Cancer Immunology and Immunotherapy
Fadi Lakkis, MD
Program(s): Cancer Immunology and Immunotherapy
Contact:
Biomedical Science Tower, W1548
200 Lothrop Street
Pittsburgh PA
Phone: 412-383-5774
Research Interests and Keywords:
  • Adaptive immunity
  • innate immunity
  • human immunology
  • immunological tolerance
Summary
The goal of Dr. Lakkis' research is to understand the fundamental mechanisms of acute and chronic rejection in solid organ transplantation. The principal areas of investigation in Dr. Lakkis' laboratory are the innate mechanisms responsible for initiating and perpetuating the alloimmune response and the role of memory T cells in allograft rejection. Dr. Lakkis' laboratory is also part of a human immunology group investigating innate and adaptive immune function in kidney transplant recipients.
Adriana Larregina, MD, PhD
Program(s): Cancer Immunology and Immunotherapy
Contact:
450 Technology Drive
Suite 300
Pittsburgh PA
Research Interests and Keywords:
  • Genetic vaccines
  • immuno-dermatology
Summary
Dr. Larregina's research interests include the study of genetic vaccines and immuno-dermatology. Sub-projects within her lab are examining: 1) generation of dendritic cell (DC) vaccines for tumors and infectious diseases; 2) skin genetic immunization; 3) DC migration out of skin and repopulation by DC precursors; and 4) modulation of specific immune responses targeting skin antigen presenting cells, and understanding the role of the skin microenvironment in modulating the function of resident DC.
Michael Lotze, MD
Program(s): Cancer Immunology and Immunotherapy
Contact:
450 Technology Drive
Suite 300
Pittsburgh PA
Binfeng Lu, PhD
Program(s): Cancer Immunology and Immunotherapy
Contact:
E1047 BST
Pittsburgh PA
Research Interests and Keywords:
  • Tumor immunology
Jason Luke
Program(s): Cancer Immunology and Immunotherapy
Marlies Meisel
Program(s): Cancer Immunology and Immunotherapy
Penelope Morel, MD
Program(s): Cancer Immunology and Immunotherapy
Contact:
E1048
Pittsburgh PA
Research Interests and Keywords:
  • Computational and mathematical models of immune responses
  • dendritic cells
  • human NK cells
Yana Najjar
Program(s): Cancer Immunology and Immunotherapy
Contact:
UPCI Research Pavilion at Hillman Cancer Center, Suite 1.32e
5117 Centre Avenue
Pittsburgh PA
Phone: 412-623-2294
Ian Pollack, MD
Program(s): Cancer Immunology and Immunotherapy
Contact:
Rangos Research Center, 6th floor
4401 Penn Avenue
Pittsburgh PA
Phone: 412-692-6580
Research Interests and Keywords:
  • Pediatric neurosurgery
  • pediatric neuro-oncology
  • brain tumor vaccines
  • craniofacial surgery
  • congenital spinal abnormalities
  • brain tumor clinical trials
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.
Hannah Rabinowich, PhD
Program(s): Cancer Immunology and Immunotherapy
Contact:
G.17c HCC
Pittsburgh PA
Research Interests and Keywords:
  • Apoptosis
  • signal transduction
Anuradha Ray, PhD
Program(s): Cancer Immunology and Immunotherapy
Contact:
UPMC Montefiore Hospital - NW628
3459 Fifth Avenue
Pittsburgh PA
Research Interests and Keywords:
  • Dendritic cell-T cell interactions
  • immune regulation
  • inflammation
  • signal transduction
Summary
Dr. Ray's primary research interest is in immune regulation of inflammatory diseases of the lung and the gut. Early research from her laboratory led to the identification of NF-kB as a target for glucocorticoid-mediated repression of gene expression and the discovery of GATA-3 as a master regulator of Th2 cells. More recent work from her laboratory has identified a key role for Tregs expressing membrane-bound TGF-beta with cross-talk with the Notch pathway in the regulation of immune tolerance in the airways.
Saumendra Sarkar, PhD
Program(s): Cancer Immunology and Immunotherapy
Contact:
Hillman Cancer Center
Lab 1.7 5117 Centre Avenue
Pittsburgh PA
Research Interests and Keywords:
  • RIG-I-like receptors (RLR)
  • interferon (IFN)-stimulated genes
  • toll-like receptor 3 (TLR3)
  • innate immune signaling
  • anti-viral innate immunity
  • type I IFN; IFN signaling
  • IFN regulatory factor 3 (IRF3)
  • tumor microenvironment
Summary
Innate immunity of an organism is the inborn protection against invading pathogens. Because it is inborn, and entrusted with the protection of the host from a vast array of previously unknown invaders, the innate immune system generates a generalized alert response upon pathogen detection. This alert is chemically mediated by a class of molecules called cytokines, such as interferons. A critical task for this host protection system is to distinguish foreign or non-self, from self, and initiate their destruction or containment. The sensors or the receptors of the innate immune system accomplish this by recognizing specific molecular patterns, which are common to pathogens or pathogen associated molecules, but absent in the host. We focus on a particular subset of these sensors/receptors, which are involved in sensing virus infection. In order to protect the host from viral invasion, the innate immune system has evolved sensors to detect foreign nucleic acids. Several unique features of virally produced DNA or RNA are exploited to distinguish viral nucleic acids from that of the host. One such unique nucleic acid is double-stranded RNA (dsRNA) ' a common byproduct or intermediate in viral genome replication. In mammals, receptors like toll-like receptor 3 (TLR3), retinoic acid-inducible gene I (RIG-I), and melanoma differentiation-associated gene 5 (MDA5) are the three known sensors of dsRNA. Single-stranded viral RNA is sensed by toll-like receptors 7 and 8 (TLR7 and TLR8), while viral DNA is detected by toll-like receptor 9 (TLR9) and other cytoplasmic receptors. We study two related aspects of the signaling process involved in interferon production in the context of infectious disease and cancer: 1) modulation of viral RNA sensing mechanisms; and 2) alternative mechanisms of interferon induction in specific tumors.
Mark Shlomchik, MD, PhD
Program(s): Cancer Immunology and Immunotherapy
Contact:
200 Lothrop St
E1040 BSTWR
Pittsburgh PA
Research Interests and Keywords:
  • B cell development
  • immunopathogenesis
Warren Shlomchik
Program(s): Cancer Immunology and Immunotherapy
Michael Shurin, MD, PhD
Program(s): Cancer Immunology and Immunotherapy
Contact:
S735, Scaife Hall
3550 Terrace Street
Pittsburgh PA
Phone: 412-648-9831
Research Interests and Keywords:
  • Tumor-induced immunomodulation
  • dendritic cells
  • cancer immunotherapy
  • psychoneuroendocrine factors of immunosuppression in cancer
Walter Storkus, PhD
Program(s): Cancer Immunology and Immunotherapy
Contact:
W1041.2 BST
Pittsburgh PA
Phone: 412-383-8643
Research Interests and Keywords:
  • Tumor biology
  • cancer vaccines
  • immunotherapy
  • gene therapy
  • dendritic cells
  • melanoma
  • renal cell carcinoma
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.
Paul Szabolcs, MD
Program(s): Cancer Immunology and Immunotherapy
Contact:
4401 Penn Avenue, Suite Floor 9
Pittsburgh PA
Research Interests and Keywords:
  • Immune reconstitution, tolerance, and alloreactivity after cord blood and bone marrow transplantation
  • immunotherapeutic strategies to prevent or treat leukemia relapse after cord blood transplantation
Angus Thomson, PhD, DSc
Program(s): Cancer Immunology and Immunotherapy
Contact:
W1544 Biomedical Science Tower (BST)
Pittsburgh PA
Phone: 412-624-6392
Research Interests and Keywords:
  • Dendritic cells
  • mTOR
  • T lymphocytes
  • immunology
Summary
Dr. Thomson's work centers on further elucidating mechanisms underlying the ability of dendritic cells (DCs) and T lymphocytes to regulate alloimmune responses. Currently, he is studying the functions of the mammalian target of rapamycin (mTOR) complex in DCs and how inhibition of mTORC1 and/or mTORC2 impacts the ability of these important antigen-presenting cells to induce and regulate T cell responses in vitro and in vivo. Studies also focus on molecular regulation of the function of liver DCs in vitro and in vivo and on their role in the promotion of liver transplant tolerance, using both experimental models and clinical material. Dr. Thomson is also testing the therapeutic potential of tolerogenic DCs and Treg in preclinical models of renal and heart transplantation.
Anda Vlad, MD, PhD
Program(s): Cancer Immunology and Immunotherapy
Contact:
204 Craft Avenue, B403
Pittsburgh PA
Phone: 412-641-2985
Research Interests and Keywords:
  • Ovarian cancer
  • immunology
  • immune surveillance
  • biomarkers
  • endometriosis
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.
Theresa Whiteside, PhD
Program(s): Cancer Immunology and Immunotherapy
Contact:
Hillman Cancer Center
1.27d
Pittsburgh PA
Research Interests and Keywords:
  • Tumor immunology
  • cancer immunotherapy
Pascal Zinn
Program(s): Cancer Immunology and Immunotherapy