Faculty
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Read More about Robert H. Vonderheide, MD, DPhilRobert H. Vonderheide, MD, DPhil
Director, Professor of Medicine
Robert H. Vonderheide, MD, DPhil
Director, Professor of Medicine
Robert H. Vonderheide, MD, DPhil, is Director, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania and the John H. Glick, MD Abramson Cancer Center’s Director Professor. Dr. Vonderheide graduated from Oxford University as a Rhodes Scholar, and Harvard Medical School. He completed training in internal medicine and medical oncology at the Massachusetts General Hospital and the Dana Farber Cancer Institute. Dr. Vonderheide is a distinguished scientist and clinician who has deciphered mechanisms of cancer immune surveillance and developed novel cancer therapeutics, particularly in pancreatic cancer. He is well-recognized for driving the development of agonist CD40 antibodies, now in later stage clinical trials as potential immune therapy of cancer.
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Read More about M. Celeste Simon, PhDM. Celeste Simon, PhD
Scientific Director
M. Celeste Simon, PhD
Scientific Director
Our laboratory studies cancer cell metabolism, tumor immunology, metastasis, and cellular responses to oxygen deprivation. The overall goal of our research is to elucidate molecular mechanisms whereby changes in O2 and nutrient availability modulate normal tissue homeostasis and mammalian pathology, with a particular focus on cancer cell metabolic reprogramming, metastasis, and interactions between malignant and infiltrating immune cells.
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Read More about Joseph R. Carver, MDJoseph R. Carver, MD
Chief Operating Officer
Joseph R. Carver, MD
Chief Operating Officer
Recognized by America's Top Doctors 2015 – 2018
Recognized by Best Doctors in America 2005 - 2012, 2015, 2016
Recognized in Philadelphia magazine's annual Top Docs issues - 2011, 2016 - 2019
Recognized in Newsweek's Best Cancer Doctors 2015
Cellular Transformation
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Read More about Craig H. Bassing, PhDCraig H. Bassing, PhD
Associate Professor of Pathology & Laboratory Medicine
Craig H. Bassing, PhD
Associate Professor of Pathology & Laboratory Medicine
The Bassing lab focuses on how to elucidate genetic, epigenetic, and biochemical mechanisms by which mammals develop their immune systems while suppressing autoimmunity and genomic aberrations that cause leukemia or lymphoma.
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Read More about Kara Bernstein, PhDKara Bernstein, PhD
George W. Raiziss Professor in Biochemistry and Biophysics II
Kara Bernstein, PhD
George W. Raiziss Professor in Biochemistry and Biophysics II
The Bernstein laboratory studies how double-strand breaks in the DNA, one of the most lethal types of DNA lesions, are repaired. By understanding the mechanism of double-strand break repair and the role of DNA repair proteins in this process, they will be able to uncover mechanisms of tumorigenesis and cancer progression. This knowledge will be used to aid in diagnosis/prognosis of different types of cancers and to find novel therapeutic targets.
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Read More about Donita C. Brady, PhDDonita C. Brady, PhD
Harrison McCrea Dickson, M.D. and Clifford C. Baker, M.D. Presidential Professor, Associate Professor of Cancer Biology
Donita C. Brady, PhD
Harrison McCrea Dickson, M.D. and Clifford C. Baker, M.D. Presidential Professor, Associate Professor of Cancer Biology
The Brady laboratory's interests lie at the intersection of cancer biology, signal transduction, and metal homeostasis.
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Read More about Eric J. Brown, PhDEric J. Brown, PhD
Associate Professor of Cancer Biology
Eric J. Brown, PhD
Associate Professor of Cancer Biology
The Brown laboratory researches the mechanisms that maintain genome stability during DNA replication and their importance in cancer treatment and aging.
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Read More about Luca Busino, PhDLuca Busino, PhD
Associate Professor of Cancer Biology
Luca Busino, PhD
Associate Professor of Cancer Biology
The Busino laboratory studies the mechanisms by which the ubiquitin-proteasome system (UPS) controls cell proliferation and how alterations in these processes contribute to tumor initiation and maintenance. Misregulation of protein degradation pathways is often observed in cancer cells. Integrating the study of cellular signals with the molecular mechanisms by which ubiquitin ligases target substrates will advance our knowledge of cancer biology and will provide novel avenues for development of therapeutics.
Areas of interest within the laboratory include, but are not limited to: (i) Signaling Pathways (such as those related to the cell division cycle, DNA damage response, circadian clock, and NFkB signaling) and (ii) Identification of small molecules to target ubiquitin ligases. -
Read More about Roger A. Greenberg, MD, PhDRoger A. Greenberg, MD, PhD
J. Samuel Staub, MD Professor of Cancer Biology
Roger A. Greenberg, MD, PhD
J. Samuel Staub, MD Professor of Cancer Biology
The Greenberg laboratory is devoted to understanding basic mechanisms of DNA repair and their impact on genome integrity, cancer etiology and response to targeted therapies. To investigate these interrelationships, we are devoted to elucidating BRCA1- and BRCA2- dependent homologous recombination mechanisms in breast and ovarian cancer, telomere length maintenance mechanisms that rely on a specialized form of homologous recombination, and DNA damage induced activation of immune responses to cancer. We utilize a myriad of approaches to investigate these areas, which include biochemistry, structural biology, cell biology, and genetically engineered mouse models.
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Read More about Sydney M. Shaffer, MD, PhDSydney M. Shaffer, MD, PhD
Assistant Professor of Pathology and Laboratory Medicine, Assistant Professor of Bioengineering
Sydney M. Shaffer, MD, PhD
Assistant Professor of Pathology and Laboratory Medicine, Assistant Professor of Bioengineering
The Shaffer laboratory works on understanding how differences between single-cells generate phenotypes such as drug resistance, oncogenesis, differentiation, and invasion, using cutting-edge technologies including high-throughput imaging, single-molecule RNA FISH, fluorescent protein tagging, CRISPR/Cas9 screening, and flow cytometry to investigate rare single-cell phenomena.
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Read More about Junwei Shi, PhDJunwei Shi, PhD
Associate Professor of Cancer Biology
Junwei Shi, PhD
Associate Professor of Cancer Biology
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, and causes up to 800,000 deaths annually worldwide. The Shi laboratory focuses on understanding molecular pathways that support HCC growth. A major clinical challenge for HCC is that most patients are diagnosed at advanced stages, and no curative treatments are currently available. The multikinase inhibitor Sorafenib is the only approved therapy for late stage HCC, which confers only an approximately 3-month median survival benefit.
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Read More about Liling Wan, PhDLiling Wan, PhD
Assistant Professor of Cancer Biology
Liling Wan, PhD
Assistant Professor of Cancer Biology
The research interests in the Wan laboratory lie in the intersection of cancer biology and epigenetics. Cancer genome studies revealed that at least 50% of human cancers harbor mutations in genes encoding epigenetic regulators. We strive to understand how epigenetic mechanisms contribute to the development and maintenance of human cancer. We are also interested in leveraging our basic mechanistic discoveries for therapeutics development. We use a host of different approaches in genetics, epigenetics, biochemistry, genome-wide sequencing, bioinformatics and functional genomics to address these questions.
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Read More about Kathryn E. Wellen, PhDKathryn E. Wellen, PhD
Professor and Vice Chair of Cancer Biology
Kathryn E. Wellen, PhD
Professor and Vice Chair of Cancer Biology
Cancer cells depend on altered nutrient uptake and metabolism to grow and divide. In order to appropriately regulate energy-intensive processes such as growth and proliferation, cells must be able to gauge their metabolic resources. The Wellen laboratory is interested in understanding how cells sense nutrient availability and integrate this information with signaling and transcriptional networks in order to modulate activities such as growth, proliferation, and differentiation. Current research focuses on elucidating the roles of nutrient-sensitive protein modifications in regulating signaling and gene expression in the contexts of cancer and metabolic disease.
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Read More about Eric S. Witze, PhDEric S. Witze, PhD
Associate Professor of Cancer Biology
Eric S. Witze, PhD
Associate Professor of Cancer Biology
The Witze laboratory studies cell polarity which is required for virtually all aspects of cell behavior including cell morphology, cell motility, and cell identity arising from asymmetric divisions (e.g., stem cells). In particular we are interested in how extracellular signals control metastatic behavior in melanoma by regulating cell polarity. Wnt5a is a non-canonical Wnt ligand that regulates cell polarity in developmental systems and we found that Wnt5a induces the formation of a novel polarized structure (WRAMP structure) in melanoma cells that mediates membrane retraction and directional cell movement. We are using live cell imaging to determine both the temporal assembly of the WRAMP structure and the function of this structure during cell migration and invasion. Future work will determine the in vivo function of the WRAMP structure and Wnt5a regulated cell polarity during metastasis.
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Read More about Xiaolu Yang, PhDXiaolu Yang, PhD
Professor of Cancer Biology
Xiaolu Yang, PhD
Professor of Cancer Biology
The Yang Lab studies the molecular and cellular mechanisms that protect against major diseases, including cancer and neurodegeneration. Our current projects are focused on three areas: 1) apoptosis pathways, 2) the tumor suppressor p53, and 3) the cellular systems that degrade misfolded proteins. Our experimental strategies include molecular and cell biology techniques, biochemical techniques, metabolic analysis, cell culture, genomics, mouse disease models, and human patient samples.
Apoptosis is a physiological process of cell auto-destruction that eliminates unwanted, damaged, or harmful cells. Dysregulation of apoptosis is associated with many diseases such as cancer, neurodegeneration, and immunodeficiency. Apoptosis is executed by the caspase family of cysteine proteases. We previously pioneered a paradigm for the activation of caspases, whereby initiator caspase activation is controlled by oligomerization. We are investigating the regulation of caspase activation in various apoptosis pathways. Paradoxically, some caspases are also involved in cell proliferation. We are studying the proliferative role of caspases to better understand the interplay between cellular life and death processes.
Tumorigenesis
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Read More about Irfan A. Asangani, PhDIrfan A. Asangani, PhD
Associate Professor of Cancer Biology
Irfan A. Asangani, PhD
Associate Professor of Cancer Biology
The Asangani laboratory employs a multidisciplinary approach to study the molecular epigenetic events associated with cancer towards the overarching goal of translating this knowledge into clinical tools by developing novel diagnostic, prognostic and therapeutic strategies. Additionally, we investigate the mechanisms of resistance to targeted therapies and develop novel combinatorial approaches that act on compensatory/new pathways in resistant tumors. Our basic strategy is to develop and deploy rational polytherapy upfront that suppresses the survival and emergence of resistant tumor cells.
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Read More about Robert BowmanRobert Bowman
Assistant Professor of Cancer Biology
Robert Bowman
Assistant Professor of Cancer Biology
I have a long-standing interest in investigating cellular behaviors and interactions in complex environments. My PhD studies in the Joyce Lab focused on uncovering the transcriptional regulation and developmental ontogeny of tumor-associated macrophages in brain tumors. As I studied the functions of myeloid cells in disease, I became increasingly interested in the epigenetic mechanisms regulating their development, and how these processes can be co-opted in leukemia. In the fall of 2016, I began my postdoctoral work with Dr. Ross Levine, setting out to model clonal evolution and clone-clone interactions in myeloid leukemias. We developed a series of novel mouse genetic tools to evaluate mutation order and oncogene-dependency using multiple, orthogonally inducible recombinases. Genomic efforts focused on single cell DNA sequencing, resulting in a comprehensive map of the genetic architecture of myeloid malignancy.
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Read More about Lewis A. Chodosh, MD, PhDLewis A. Chodosh, MD, PhD
Perelman Professor and Chair in Cancer Biology
Lewis A. Chodosh, MD, PhD
Perelman Professor and Chair in Cancer Biology
Breast cancer is the most common cancer as well as the leading cause of death from cancer among women worldwide. The Chodosh laboratory uses genetically engineered mouse models, patient samples and computational biology to study the mechanisms by which breast cancers develop, become resistant to therapy, and ultimately contribute to cancer mortality. A broad array of basic and translational research approaches are used to address problems of fundamental clinical importance to cancer patients by elucidating pathways and principles common to human cancers. Particular areas of interest include: pathways regulating cancer development, metastasis, tumor dormancy and recurrence; the use of genomics and computational approaches to understand genetic programs in cancer; the impact of obesity on cancer recurrence; the mechanisms by which pregnancy protects against breast cancer; and the use of non-invasive imaging approaches to study tumor biology. These approaches employ molecular, cellular, animal, human, and in silico model systems to study the function of key regulatory molecules in tumor biology using genetics, genomics, molecular biology, biochemistry, cell biology, computational biology, functional imaging, animal studies, preclinical trials and clinical investigation.
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Read More about David M. Feldser, PhDDavid M. Feldser, PhD
Director, CAMB Cancer Biology Ph.D. Program, Associate Professor of Cancer Biology
David M. Feldser, PhD
Director, CAMB Cancer Biology Ph.D. Program, Associate Professor of Cancer Biology
The Feldser laboratory uses genetically engineered mouse models to study tumor progression and metastasis of common forms of human cancer. These models faithfully recapitulate many aspects of the histopathological progression of their human counterparts. Tumors initiate as lesions within the appropriate tissue microenvironment from single cells due to induced activation of latent oncogenes and/or deletion of key tumor suppressor genes. These lesions evolve through multiple cellular states toward malignant and metastatic disease. Our research is dedicated to deconstructing the multistep process of tumorigenesis.
The major emphasis of the Feldser laboratory is to uncover the pathways that are disabled by mutational inactivation of tumor-suppressor genes as well as those pathways stimulated by aberrant oncogene activation. We focus on mouse models in order to employ novel genetic tools to regulate gene function in developing cancerous lesions as well as to track cancer growth and dissemination via bioluminescent and fluorescent techniques. We couple cellular, genomic and biochemical analyses to our powerful in vivo tools to discern the mechanics of tumor progression and metastasis with the goal of identifying new therapeutic strategies to eradicate malignant cells.
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Read More about Malay Haldar, MD, PhDMalay Haldar, MD, PhD
Associate Professor of Pathology & Laboratory Medicine
Malay Haldar, MD, PhD
Associate Professor of Pathology & Laboratory Medicine
The Haldar laboratory's research is at the intersection of innate immune system and solid tumor biology. Specifically, the lab studies the mononuclear phagocyte system (MPS) with an emphasis on their role in the tumor microenvironment. MPS is part of the innate immune system and comprises of monocytes, macrophages, and dendritic cells (DC). These cells are functionally, phenotypically, and developmentally heterogeneous with many distinct subsets. We are interested in understanding the molecular basis of this developmental and functional heterogeneity within the MPS. A major focus in our laboratory is to understand the role of MPS within the microenvironment of a group of solid tumors known as sarcomas. DCs and macrophages are thought to play important role in cancer by modulating host-immune responses against the tumor cells, promoting metastasis, angiogenesis, etc. Additionally, the ability of these cells to regulate lymphocyte function makes them an important determinant in the success of cancer immunotherapy. Using a combination of advanced genetically engineered mouse models in conjunction with patient-derived samples, they aim to uncover the molecular pathways underlying tumor-MPS interaction with the overarching goal of targeting them for therapeutic purposes.
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Read More about Xianxin Hua, MD, PhDXianxin Hua, MD, PhD
Professor of Cancer Biology
Xianxin Hua, MD, PhD
Professor of Cancer Biology
The Hua laboratory's research focuses on elucidating the molecular mechanisms whereby menin, a scaffold protein interacting with multiple epigenetic regulators, regulates endocrine cells, including pancreatic beta cells, endocrine tumors, and MLL fusion protein-induced leukemia. In particular, we are interested in dissecting the function of menin, which is mutated in hereditary human tumor syndrome, Multiple Endocrine Neoplasia Type 1 (MEN1), in repressing beta cells and endocrine tumors and in promoting leukemogenesis.
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Read More about Chengcheng Jin, PhDChengcheng Jin, PhD
Assistant Professor in Cancer Biology
Chengcheng Jin, PhD
Assistant Professor in Cancer Biology
The development of cancer involves not only intrinsic genetic alterations in tumor cells but also the failure of immune surveillance and unresolved inflammation; yet it is not well understood how host-intrinsic or environmental factors direct the immune response towards tumor-promoting inflammation versus anti-tumor immunity. The Jin lab studies the fascinating interplay between the host immune system, commensal microbiota and developing tumor cells using genetically engineered mouse cancer models. Specifically, the goals of our projects are: (1) Understanding how immune responses initiate and evolve over time as tumors arise de novo and progress; (2) Defining the molecular and cellular mechanisms by which the immune system senses and responds to microbiota-derived or tumor-intrinsic signals in the tumor microenvironment to regulate tumor growth and cancer responses to therapies.
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Read More about Brian D. Keith, PhDBrian D. Keith, PhD
Adjunct Professor of Cancer Biology
Brian D. Keith, PhD
Adjunct Professor of Cancer Biology
Dr. Brian Keith has played an integral role in the AFCRI as former Education Officer leading efforts with Biomedical Graduate Studies (BGS) and the Biomedical Postdoctoral Programs (BPP) implementing and sustaining programs for AFCRI trainees. He currently works with Wistar faculty to guide educational efforts at all levels of training, from high school students to postdoctoral fellows. These programs include the Summer Fellowship in Biomedical Research, an eight-week intensive program that introduces high school students to biomedical research as they work on active projects in the lab. Another program is the Biomedical Technician Training Program (BTT), which prepares Community College of Philadelphia (CCP) students for careers in academic or commercial research labs. In addition, the newly launched Biomedical Research Training Apprenticeship (BRT)—a spinoff from the BTT Program—offers longer internships and additional on-the-job training. BRT is the first registered, nontraditional apprenticeship program to offer students a pathway to become medical research technicians ratified by the Pennsylvania Department of Labor & Industry, and is the first of its kind in the nation.
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Read More about Ronen Marmorstein, PhDRonen Marmorstein, PhD
George W. Raiziss Professor and Vice-Chair, Department of Biochemistry and Biophysics
Ronen Marmorstein, PhD
George W. Raiziss Professor and Vice-Chair, Department of Biochemistry and Biophysics
The Marmorstein laboratory studies the molecular mechanisms of protein post- and co-translational modification with a particular focus on protein acetylation and phosphorylation and chromatin regulation. The laboratory uses a broad range of molecular, biochemical and biophysical research tools centered on macromolecular structure determination using X-ray crystallography and cryo-electron microscopy. The laboratory is particularly interested in gene regulatory proteins and their upstream signaling kinases that are aberrantly regulated in cancer and other age-related disorders, and the use of high-throughput small molecule screening and structure-based design strategies towards the development of protein-specific small-molecule probes to be used to further interrogate protein function and for development into therapeutic agents.
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Read More about Andy J. Minn, MD, PhDAndy J. Minn, MD, PhD
Professor of Radiation Oncology
Andy J. Minn, MD, PhD
Professor of Radiation Oncology
A vast majority of human tumors express interferon-stimulated genes (ISGs), indicating that the activation of pathways controlling the induction of ISGs is a pervasive feature of cancer. Typically, ISGs result from pathogens, such as viruses, that are recognized by a class of receptors called pattern recognition receptors (PRRs). This leads to the induction of the anti-viral cytokine interferon (IFN). In the context of viral infection, this anti-viral response has many effects that include direct anti-pathogen function, regulation of innate and adaptive immune responses, and control of tissue regeneration. However, in the case of cancer, the engagement of PRRs and subsequent expression of ISGs is generally not due to virus infection but rather endogenous molecules in cancer cells and/or the tumor microenvironment that mimic viruses. A main focus of the Minn Laboratory's research is to understand: 1) the nature of the endogenous molecules in cancer cells or the tumor microenvironment that can mimic viruses, 2) why cancer cells evolve to recognize endogenous molecules as they would foreign pathogens, 3) what function this serves, and 4) the clinical/translational relevance of this "virus mimicry".
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Read More about Warren S. Pear, MD, PhDWarren S. Pear, MD, PhD
Professor of Pathology & Laboratory Medicine
Warren S. Pear, MD, PhD
Professor of Pathology & Laboratory Medicine
A major area of interest of the Pear laboratory is understanding the processes that lead to the development and differentiation of mature hematopoietic cells from a single hematopoietic stem cell. We are particularly interested in studying the processes that perturb these normal processes and cause leukemia. A primary focus of the laboratory is the role that Notch proteins play in regulating hematopoietic cell fate decisions and cancer. Notch proteins are a conserved family of receptors that regulate cell fate decisions in organisms ranging from Drosophila to humans. Using a variety of in vitro and in vivo approaches, we have shown that Notch proteins are key regulators of multiple hematopoietic cell fates. These include establishment of the T cell lineage and helper type 2 T cells.
The Pear laboratory are presently undertaking studies to identify the signaling pathways that control these and other cell fate decisions in hematopoiesis. In addition to their role in normal hematopoiesis, dysregulation of Notch signaling is a cause of human leukemia. We have developed a mouse model of Notch-related leukemia and are using this to study the signaling pathways that lead to oncogenic transformation. Using gene array and bioinformatics approaches, we have identified several direct transcriptional targets of Notch signaling that appear to mediate its effects in normal development and leukemia. In addition, we are developing and testing ways to block Notch signaling that may be useful in treating leukemia and other Notch-dependent diseases.
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Read More about M. Celeste Simon, PhDM. Celeste Simon, PhD
Arthur H. Rubenstein, MBBCh Professor of Cell and Developmental Biology
M. Celeste Simon, PhD
Arthur H. Rubenstein, MBBCh Professor of Cell and Developmental Biology
Our laboratory studies cancer cell metabolism, tumor immunology, metastasis, and cellular responses to oxygen deprivation. The overall goal of our research is to elucidate molecular mechanisms whereby changes in O2 and nutrient availability modulate normal tissue homeostasis and mammalian pathology, with a particular focus on cancer cell metabolic reprogramming, metastasis, and interactions between malignant and infiltrating immune cells.
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Read More about Nancy A. Speck, PhDNancy A. Speck, PhD
Professor and Chair, Department of Cell & Developmental Biology
Nancy A. Speck, PhD
Professor and Chair, Department of Cell & Developmental Biology
The Speck laboratory primarily researches the core binding factor (Runx1-CBFβ) and its roles in hematopoietic stem cell (HSC) formation and function. We study how HSCs form in the embryo, the step at which HSC formation is dependent on Runx1-CBFβ, the biochemical functions of Runx1-CBFβ, and how mutations in the genes encoding Runx1-CBFβ generate pre-leukemic stem cells. A more recent line of investigation is to determine the role of inflammatory signaling in HSC formation.
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Read More about Ben Z. Stanger, MD, PhDBen Z. Stanger, MD, PhD
Hanna Wise Professor of Cancer Research, Professor of Medicine
Ben Z. Stanger, MD, PhD
Hanna Wise Professor of Cancer Research, Professor of Medicine
During development, cells acquire specialized features through a series of differentiation events. Under normal circumstances, adult cells retain their differentiated identities. However, under a variety of experimental and physiological situations, cell identity can shift. This adult cell plasticity can involve an interchange between adult cellular identities (termed "trans-differentiation") or a reversion from a specialized state to a progenitor stated (termed "de-differentiation"). The Stanger laboratory uses genetically engineered mice to understand how cell identity is maintained in vivo. We study cellular plasticity in the context of liver regeneration, diabetes, and cancer - where epithelial-to-mesenchymal transition promotes cell invasion and metastasis. In addition, we have a strong interest in tumor immunology, and the mechanisms by which tumor cells influence their microenvironment. We believe that the ability to manipulate cellular identity in these settings will facilitate the development of novel therapies for cancer and degenerative disease.
Translational Research
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Read More about Robert Babak Faryabi, PhDRobert Babak Faryabi, PhD
Associate Professor of Pathology & Laboratory Medicine
Robert Babak Faryabi, PhD
Associate Professor of Pathology & Laboratory Medicine
The Faryabi lab focuses on understanding the mechanism of epigenetic dysregulation in cancer. We are particularly interested in elucidating how oncogenic signals contribute to tumor pathogenicity through epigenetic misregulation, and to leverage this mechanistic understanding for improved treatments.
The lab mainly studies cancers with frequent mutations in Notch receptor families. We use combination of wet and dry techniques to understand how oncogenic Notch drives regulatory program in these tumors. Our lab benefits from various established data-rich assays and combine them with novel technologies such as chromatin conformation and single cell genomics to elucidate the mechanisms of epigenetic dysregulation in Notch-driven tumors at both population and single cell levels.
As a member of Center for Personalized Diagnostics, we are also developing computational oncology frameworks to enrich clinical significance of diagnostic tumor genomics. Our goal is to advance the paradigm of personalized medicine by leveraging big data analytics to drive correlation between the tumor genomes and clinical covariates. -
Read More about Terence P. Gade, MD, PhDTerence P. Gade, MD, PhD
Associate Professor of Radiology
Terence P. Gade, MD, PhD
Associate Professor of Radiology
Dr. Terence Gade leads the Penn Image-Guide Intervention Lab. Interventional oncology represents the fourth arm of cancer therapy offering locoregional treatment approaches for a variety of malignancies. These approaches apply minimally invasive procedures to target cancer using percutaneous or endovascular techniques. In using imaging to directly modulate the tissue environment of the targeted cancer, these techniques provide a unique lens through which to study the tumor microenvironment. The tumor microenvironment comprises complex interactions between cancer cells and the stroma including immune cells, fibroblasts, the extracellular matrix as well as vascular networks. Our interests focus broadly on the study of the tumor microenvironment and how alterations in the tumor microenvironment affect subpopulations of cancer cells as well as how they influence the interactions of stromal cells with the tumor. Given that these are in vivo phenomena, the development of novel in vivo molecular imaging strategies is implicit in order to characterize these interactions. These studies will lead to new therapeutic targets and imaging strategies that can be applied for new and improved interventions. Current projects in the lab emphasize this goal in the context of a variety of disciplines including molecular biology, metabolism, immunology, bioengineering and imaging physics. Visit the lab here.
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Read More about Carl H. June, MDCarl H. June, MD
Richard W. Vague Professor in Immunotherapy, Professor of Pathology and Laboratory Medicine
Carl H. June, MD
Richard W. Vague Professor in Immunotherapy, Professor of Pathology and Laboratory Medicine
The June Lab is primarily responsible for developing new CARs and new vectors for current and proposed indications. This lab also fosters the development of Penn students both in doctoral and post-doctoral programs. The June Laboratory provides researchers with the tools they need to translate laboratory insights into safe and effective cancer therapies. The June Laboratory works with University of Pennsylvania faculty members interested in moving biologically-focused research ideas into clinical trials. In addition, the June Laboratory has a cadre of faculty researchers focused on developing ways to enhance the ability of the natural immune system to recognize and eliminate tumor cells. Translational research is a core unit of the The Leonard and Madlyn Abramson Family Cancer Research Institute at the Abramson Cancer Center at the University of Pennsylvania. Created in December 1997 with a $100 million pledge from the Abramson Family Foundation, the Cancer Research Institute integrates research, education, and comprehensive patient care at the Abramson Cancer Center at the University of Pennsylvania. For more information, see the Translational Research Mission Statement.
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Read More about Ivan Maillard, MD, PhDIvan Maillard, MD, PhD
Professor of Medicine
Ivan Maillard, MD, PhD
Professor of Medicine
The Maillard laboratory investigates the regulation of normal and malignant hematopoiesis, bone marrow transplantation and T cell alloimmunity. A central focus of their studies is the role of Notch signaling in T cell development, differentiation and function. Using mouse models of bone marrow transplantation, they discovered essential functions for Notch receptors and ligands in graft-versus-host disease with a high fundamental and translational impact. The Maillard laboratory is also interested in understanding the role of Trithorax family epigenetic regulators in hematopoiesis and leukemia.
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Read More about John Matthew Maris, MDJohn Matthew Maris, MD
Giulio D'Angio Professor of Pediatric Oncology
John Matthew Maris, MD
Giulio D'Angio Professor of Pediatric Oncology
Dr. Maris developed his laboratory and a translational research program at Children's Hospital to help us focus on the genetic abnormalities in hereditary and sporadic neuroblastoma. They strive to be the world’s leading neuroblastoma research and treatment center as we work to exponentially increase our understanding of this cancer and its underlying biology.
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Read More about Vikram Paralkar, MDVikram Paralkar, MD
Assitant Professor of Medicine, Division of Hematology-Oncology
Vikram Paralkar, MD
Assitant Professor of Medicine, Division of Hematology-Oncology
The Paralkar laboratory studies how genes regulating ribosome biogenesis guide normal hematopoiesis, and how mutations in these genes lead to acute or chronic myeloid leukemias. Hematopoiesis is a complex and highly regulated process by which stem cells residing in bone marrow produce a constant stream of blood cells to preserve a functional hematopoietic system throughout the duration of a human lifespan. Mutations in epigenetic regulators, transcription factors, splicing proteins and tumor suppressors can derange the normal course of hematopoiesis, and lead to clonal expansion and leukemia. Several mutated proteins also regulate ribosomal biogenesis. Normal ribosomal function is crucial for hematopoiesis, and dysfunction can either lead to bone marrow failure or myeloproliferation. The mechanisms by which most of these mutated genes produce malignancy remain poorly understood.
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Read More about James L. Riley, PhDJames L. Riley, PhD
Professor of Microbiology
James L. Riley, PhD
Professor of Microbiology
The Riley laboratory studies the signals that control primary human T cell activation and function with special attention to how these manipulations can be exploited to develop T cell therapies for HIV, autoimmune disease and cancer. We are studying how to best re-direct and expand human T regulatory cells for use in the treatment of autoimmune disease. We are evaluating both the use of TCR and CARs to redirect Tregs and studying both how these methods provide antigen suppression and if these approaches alter T regulatory cell stability. Part of this research is studies to understand how altering the media by which T cells are expanded in alters their function and engraftment potential in vivo. These studies have spurred interested on how various metabolic pathways are perturb by external signaling and environment. The lab is also focused on designing HIV resistant, HIV specific T cells to be key players in the HIV Cure effort. As a leader of the BEAT HIV Martin Delaney Collaboratory his lab is evaluating ways to make T cells resistant to HIV entry and integration and developing HIV-1 specific chimeric antigen receptors to evaluate the ability of these T cells to control HIV replication in both in vitro and humanized mouse studies. Dr. Riley’s basic research findings using primary human T cells have been used as the basis and rationale for numerous Phase I adoptive T cell therapy clinical trials.
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Read More about Robert H. Vonderheide, MD, DPhil
Robert H. Vonderheide, MD, DPhil
John H. Glick Abramson Cancer Center Professor
Robert H. Vonderheide, MD, DPhil
John H. Glick Abramson Cancer Center Professor
The Vonderheide laboratory combines efforts in both basic research and clinical investigation to advance the understanding of tumor immunology and to develop novel immunotherapies for cancer. The chief hypothesis is that successful approaches in tumor immunotherapy will need to (a) optimize target antigens with regard to clinical applicability and risk of antigen loss, (b) repair host immuno-incompetence in antigen presentation and T cell function, and (c) circumvent immuno-suppressive factors of the tumor and tumor microenvironment.
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Read More about Alexander Huang, MDAlexander Huang, MD
Assistant Professor of Medicine
Alexander Huang, MD
Assistant Professor of Medicine
Alex’s research program focuses on translational cancer immunology research, taking advantage of innovative clinical trials to 1) identify targets for novel immunotherapies in cancer, 2) understand mechanisms of response and resistance, and 3) ultimately to implement precision immuno-oncology in the clinic. His research involves the integration of immunotherapy trials, flow cytometric and transcriptional approaches, and advanced computational analysis to understand the underlying cellular mechanism of immunotherapies in the human system. Specifically, he has a long-standing interest on the pharmacodynamic immune responses of immune checkpoint blockade.
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Read More about Kara Maxwell MD, PhD
Kara Maxwell MD, PhD
Assistant Professor of Medicine
Kara Maxwell MD, PhD Website
The Maxwell Lab is a translational human genetics and genomics laboratory. Dr. Maxwell is a cancer genetics trained oncologist, regional referral expert for patients with Li Fraumeni Syndrome (LFS), and the Director of the Basser Center for BRCA Men and BRCA program. The lab leverages Dr. Maxwell’s patient population to study hereditary breast and prostate cancer. The lab uses cell line and mouse models in addition to multi-omics analyses of human tissues to study early breast and prostate cancer development and progression due to inherited mutations in TP53 and BRCA2. In addition, the lab uses large scale datasets such as the Penn Medicine Biobank and the Million Veterans Program to determine novel genetic risk factors for breast and prostate cancer and to perform genotype-phenotype analyses in known cancer risk syndromes.
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Read More about Dana Silverbush, PhDDana Silverbush, PhD
Assistant Professor of Cancer Biology, Assistant Professor of Neurosurgeryv
Dana Silverbush, PhD
Assistant Professor of Cancer Biology, Assistant Professor of Neurosurgeryv
The Silverbush Lab
Tumors are complex and heterogeneous systems, which challenge their classification and treatment. The Silverbush lab decodes tumor heterogeneity and plasticity to understand how cancer cells transform to become more aggressive or evade treatment. We particularly examine hard-to-treat cancers with high heterogeneity, focusing on the notorious kings of heterogeneity and aggressiveness: brain cancers.
To achieve this goal, we develop and implement multi-omic single-cell tools. These tools enable us, for the first time, to simultaneously measure DNA methylation, point mutations, and transcriptional activity in the same single cells. To tackle these complex goals, we build an interdisciplinary team, welcoming MDs, biologists, immunologists, computational biologists, and pure computer scientists focusing on ML and AI. The lab encompasses wet lab and computational components, managing complex algorithmic and wet lab challenges, translational applications, and working closely with clinicians.
On-going and future projects (including rotation opportunities):
Deciphering Tumor Evolution Using Multi-omic Single Cells: Tumors are complex systems, heterogeneous on multiple levels. We can observe their patterns of heterogeneity at the transcriptomic, genetic, and epigenetic levels. However, we lack an understanding of how these levels work in conjunction or how they contribute to treatment resistance. In this project, we measure point mutations and the transcriptome from the same single cell, using the newest technique we developed, and analyze the data to uncover various layers of heterogeneity and establish connections between them.
Explore Clinical Trials through the Lens of Tumor Heterogeneity: For decades, teams have attempted to discover effective treatments for GBM and have tested therapeutics within the framework of clinical trials. Currently, no GBM clinical trial has demonstrated substantial improvement. The hypothesis is that these treatments may be effective only on a subset of patients or a subset of cells, depending on their tumor composition. In this effort, we build both experimental techniques and computational ML solutions to examine the changes in tumor and microenvironment through treatment. Specifically, we are investigating the alterations in tumor composition and the infiltration of T cells following the novel cutting-edge CART T cell therapy.
ML Solutions for Accurate Diagnosis and Prognosis: A key obstacle in cancer treatment is administering the right drug at the right time, before the target becomes obsolete. This has proven crucial in IDH mutant glioma, with the first-ever IDH mutant glioma successful clinical trials to treat these tumors showing efficacy when given early enough to patients. What is early enough? This is still largely unknown, as these tumors progress and change their composition in yet-to-be-discovered patterns. In the project, we design and implement novel ML solutions to identify the pattern of multi-omic longitudinal changes in patient samples. This approach aims to first decipher the evolution of these tumors and second, provide an actionable tool used by our collaborators around the world to obtain an accurate diagnosis and pinpoint the correct point of therapeutic intervention.
For further reading, please check out:
- Multi omic single cell studies to decipher tumor heterogeneity and plasticity: Epigenetic encoding, heritability and plasticity of glioma transcriptional cell states
- Computational biology to correct tumor classification and prognosis: Predict tumor composition from bulk DNA methylation profile
Lab Personnel
Nelson (Trip) Freeburg - Postdoctoral Fellow
Jacqueline (Jackie) Peng - PhD Student
Megan Costa - PhD Student
Daniel Chafamo - MD Student
Gayathri Konanur - Lab Manager
- Multi omic single cell studies to decipher tumor heterogeneity and plasticity: Epigenetic encoding, heritability and plasticity of glioma transcriptional cell states
