- Professor-in-Residence, UCSF Helen Diller Family Comprehensive Cancer Center and Department of Anatomy
- Director, Preclinical Therapeutics Core Facility, UCSF Helen Diller Family Comprehensive Cancer Center
RESEARCH AREAS
The Akhurst lab undertakes basic studies on the genetics and biology of TGFβ signaling in vivo using mouse models of cancer and angiogenesis. This includes preclinical investigation of both large and small molecule inhibitors of TGFβ signaling for oncology using chemically-induced mouse models that have complex genetic repertoires similar to those of human tumors, a particularly attractive model for studies on immunotherapy. A major interest in the lab is investigation of how germline and somatic genetic variation can influence the outcome of TGFβ inhibition, both as monotherapy and in combination with checkpoint inhibitors. A more basic interest is in identify genetic interactions with TGFβ signaling that influence in vivo phenotypes as a route to identify novel drug targets, as well as predictors of response to TGF blockade.
The Akhurst lab also studies rare diseases caused by mutations in genes encoding components of the TGFβ/BMP signaling pathway, such as the vascular disorder, Hereditary Hemorrhagic Telangiectasia. It is anticipated that these studies will drive understanding on how interacting genetic variants influence the severity of this human disease, and will provide insight into mechanisms of in vivo angiogenesis and vascular stability in humans. A deeper understanding of the genes responsible for variable outcome of TGFβ pathway manipulation could contribute to development of novel drugs or drug-dosing regimens for a number of diseases that involve the TGFβ/BMP signaling pathway.
Akhurst Lab: http://cancer.ucsf.edu/research/akhurst-lab
- Co-Leader, Cancer Genetics Program
- Director, Genome Analysis Core Facility, UCSF Helen Diller Family Comprehensive Cancer Center
RESEARCH AREAS
The Balmain lab’s research focus has been the elucidation of the molecular mechanisms of multistage carcinogenesis, with particular emphasis on mouse models of chemically induced skin tumor development, but also including lung, prostate and lymphoid tumors. They have generated mouse models that recapitulate the genetic heterogeneity of human populations and use those models to identify the sequence of somatic genetic alterations, which are associated with discrete stages of tumorigenesis: Initiation àPromotion àProgression to locally invasive lesions àDevelopment of metastases. They have developed cell lines from tumors representing each of these stages of carcinogenesis, and in some cases have characterized cells from successive stages of development from the same tumor. These have proved invaluable for studies of the causal genetic and biological changes associated with tumor progression. The results have shown that the kinds of genetic and biological alterations seen in mouse tumors are very similar to what is observed in human malignancies, thus providing strong evidence that the mouse is a uniquely appropriate model for the development of cancer in humans. In particular, it has been shown by genome sequencing that mouse tumors of the skin or lung that are induced by chemical exposures closely resemble human tumors of the lung, skin or colon that are associated with exposure to environmental agents. The point mutations in these chemically induced tumors, which are generally not seen in genetically engineered mouse cancer models, are an important determinant of responses to therapy, specifically immunotherapy which is dependent on the expression of novel tumor antigens in highly mutagenized tumors. The goal for the next few years is to exploit mouse model systems for the identification of genes that are important for cancer susceptibility or cancer progression in human populations, and for development and characterization of novel approaches to cancer therapy.
Balmain Lab: http://cancer.ucsf.edu/research/balmain-lab
- A.W. and Mary Margaret Clausen Distinguished Professor, School of Medicine
- Director, Hormone Research Institute, Diabetes Center
- President & CEO, Parker Institute for Cancer Immunotherapy
RESEARCH AREAS
The Bluestone Lab research over the past 25 years has focused on understanding the basic processes that control T cell activation and immune tolerance in autoimmunity and organ transplantation. He and members of his lab have developed soluble receptor antagonists; monoclonal antibodies and animals deficient in individual members of TCR and co-stimulatory pathways to define their individual roles in transplant rejection and autoimmunity including a special emphasis on a specialized subset of T cells termed “regulatory T cells” (Treg). Tregs control fundamental aspect of immune homeostasis. During the last several years, his research has adapted the animal studies using biologics and cell based therapies to develop therapeutics that can be used in humans with autoimmunity and under conditions of allotransplant rejection. Finally, his lab initiated several projects to determine mechanisms that control Treg stability and has developed novel approaches to destabilize Tregs in cancer settings to promote anti-tumor immunity.
Bluestone Lab: http://bluestone.ucsf.edu
- HS Clinical Professor, Department of Medicine (Hematology/Oncology)
- Director, Melanoma Clinical Research, UCSF Helen Diller Family Comprehensive Cancer Center
RESEARCH AREAS
Dr. Daud’s group at UCSF is focused on developing and evaluating both targeted therapeutics as well as immunotherapy agents for the treatment of melanoma. His research has been heavily involved in immunotherapy. They developed IL-12 gene therapy in melanoma and carried out the first in human clinical trial in 2005-2007. Based on this work, IL-12 electroporation is being explored in many cancers as an immune agent and as a combination treatment with anti- PD-1 and other checkpoint inhibitors in melanoma. He was involved in developing PD-1 in the clinic including the first in human trial of pembrolizumab. Furthermore, he and colleagues at UCSF have developed a novel assay that profiles the intra-tumoral microenvironment in depth and can predict non- response to the checkpoint inhibitors, such as anti-PD-1. They are using this and other assays to better understand melanoma disease biology and mechanisms of resistance and metastasis. Dr. Daud has very robust clinical research program and has been the principal investigator on numerous clinical trials.
- Professor, School of Medicine
- Leader, Cancer Immunotherapy Program, UCSF Helen Diller Family Comprehensive Cancer Center
- Co-Director, UCSF Parker Institute for Cancer Immunotherapy
RESEARCH AREAS
The Fong Lab research focuses on how the immune system interacts with cancer as well as exploring tumor immunotherapies in both mouse models and in patients. While their studies frequently transcend different tumor types, they are particularly focused on immunotherapy of GI and GU malignancies. They described the immunogenicity of prostate acid phosphatase (PAP), which is the target antigen for sipuleucel-T, now an FDA-approved immunotherapy for prostate cancer. Dr. Fong early work in immune checkpoint inhibitors involved participating in the first-in-man clinical trials with ipilimumab, an anti-CTLA4 antibody that is now FDA approved for melanoma. His lab continues to investigate how immunotherapies such as immune checkpoint inhibitors and cancer vaccines can enhance anti-tumor immunity in patients systemically as well as in the tumor microenvironment. By performing neoadjuvant immunotherapy trials, they are determining how specific therapies can recruit immune effectors in vivo in cancer patients. Moreover, they have studied how clinical responders may differ from clinical non-responders. They are applying unbiased approaches to studying antigen-specific responses that are modulated in these patients and are currently developing biomarkers that may be predictive of clinical efficacy. They also utilize autoimmune prone mouse models to define tumor-associated antigens, which may represent novel vaccine candidates.
Fong Lab: http://hemonc.ucsf.edu/fonglab/
- Professor, Department of Pathology, UCSF
RESEARCH AREAS
The Krummel Lab focuses on understanding patterns of immune cell-cell interactions and how these generate “the immune system”. Over the past ten years, they have developed novel imaging technologies and computational platforms to understand immunological processes in space and in time within normal and diseased organs. They were the first to live-image events in progressive tumors in which incoming tumor-specific T cells are captured by a population of myeloid cells and the lab is developing protein immuno-therapeutics using imaging to ‘guide’ this development.
The lab also has a fundamental interest in how T cells become activated. This involves a specialized 'immune synapse' formed between T cells and their antigen-presenting partner cells. Their studies of the immune synapse have shown how T cells regulate their motility in order to effectively 'search' for their antigens. They have also demonstrated how T cells signal through synapses while moving through organs and how T cells communicate with each other when they arrest. Finally, they have recently developed imaging technologies that allow, for the first time, observation of the immune system in the homeostatic, infected/injured, allergic or metastatic lung.
Krummel Lab: http://pathology.ucsf.edu/krummel/
- American Cancer Society Professor
- The J. Michael Bishop, MD, Distinguished Professor and Chair of Microbiology and Immunology
- Leader, Cancer Immunity Program, UCSF Helen Diller Family Comprehensive Cancer Center
- Director, UCSF Parker Institute for Cancer Immunotherapy
RESEARCH AREAS
The Lanier Lab research focuses on dissecting out the biology of natural killer (NK) cells in immune responses and in particular on the activity that NK inhibitory and activating receptors play in allowing NK cells to distinguish cells that are transformed or infected with viruses from healthy cells. His lab has identified many of the activating and inhibitory NK receptors (NKR), their ligands, and signaling pathways and defined their role in innate and adaptive immune responses to pathogens and cancer. The lab has developed numerous mouse models systems in order to explore the physiological role of these NK receptors in resistance to viral infections (cytomegalovirus, poxviruses, and influenza) and primary tumorigenesis.
Recently, the Lanier lab has been focusing on how activating NKRs can drive the expansion, differentiation, and generation of immunological memory, both in NK cells and T-cells. In particular, they are examining the role of activating NKRs on the TcR-dependent adaptive responses and TcR-independent innate responses of memory T cells, the fate of NK cells following immune challenge with pathogens or tumors and understanding the role of NKRs in the generation of immunological memory in NK cells. The concept that NK cells can acquire immunological memory and mediate enhanced responses upon re- encountering pathogens provides a new paradigm that might be exploited in the therapeutic treatment of infectious diseases and cancer.
Lanier Lab: https://lanierlab.ucsf.edu
- Professor, Department of Anesthesia
Liu Lab: http://liulab.ucsf.edu/Home_Page.html
- Professor of Neurological Surgery
- Director, UCSF Brain Tumor Immunotherapy Center
RESEARCH AREAS
Dr. Okada is a physician–scientist dedicated to development of effective immunotherapy for brain tumor patients for over 20 years. His team was one of very first to discover cytotoxic T lymphocyte (CTL) epitopes in glioma-associated and glioma-specific antigens. Dr. Okada also found critical roles for the integrin receptor very late activation antigen (VLA)-4 and the chemokine CXCL10 in facilitating entry of CTLs to the brain tumor site. Dr. Okada has translated these discoveries into a number of innovative immunotherapy clinical studies, such as one with chimeric antigen receptor (CAR)-transduced T-cells, in both adult and pediatric brain tumor patients. In addition to institutional and bi-institutional trials, Dr. Okada’s discoveries have led to two currently active multicenter trials (NCT02078648 and NCT02960230), each involving 10 or more sites. A majority of midline infiltrating glioma (MIG) cases harbor the amino acid substitution from lysine (K) to methionine (M) at position 27 of the histone 3 variant H3.3 (K27M). This K27M mutation is associated with shorter survival. Dr. Okada’s lab is evaluating K27M as a novel, shared neoantigen epitope for effective and safe T-cell-based immunotherapy or as peptide for vaccine therapies. Furthermore, Dr. Okada leads an international group of brain tumor immunotherapy experts to develop novel iRANO criteria. In addition to development of novel immunotherapy approaches, Dr. Okada’s team has also pioneered in discoveries of novel immunoregulatory mechanisms in gliomas, such as one mediated by myeloid-derived suppressor cells (MDSC) and mutations of the isocitrate dehydrogenase (IDH) enzymes IDH1 and IDH2.
- Professor, Department of Medicine, Hematology/Oncology
- Professor, Departments of Neurology, Pediatrics, and Neurological Surgery
- Co-Leader, Pediatric Malignancies Program, Helen Diller Family Comprehensive Cancer Center
RESEARCH AREAS
Dr. Weiss's research is focused on neural tumors, including medulloblastoma, neuroblastoma, and glioma. Collectively, these tumors account for nearly one-third of childhood cancer deaths each year. Pediatric tumors are an important challenge for immuno-oncology because they often have fewer tumor-specific mutations compared to adult tumors. Dr. Weiss's lab has developed a number of immune-competent mouse models of neural tumors, allowing the preclinical testing of immunotherapies and targeted inhibitors and mechanistic studies of the infiltrating immune cells. The Weiss Lab also has a longstanding interest in studying and targeting the MYCN and EGFR oncogene, prominent drivers of tumor progression and immune evasion in neural tumors. The lab uses high-dimensional single-cell approaches to understand the immune microenvironment of both mouse and human tumors, and uses mouse models to investigate new therapeutic approaches. The ultimate goal of these efforts is to identify new therapies that improve outcomes and reduce morbidity for patients with these tumors.
Weiss Lab: http://waweisslab.ucsf.edu
- UCSF Sandler and Sean N. Parker Faculty Fellow
RESEARCH AREAS
Dr. Spitzer’s research is focused on developing improved experimental and analytical methods to model the state of the immune system using high dimensional single-cell data. His work led to the first reference map of the immune system, providing a framework into which new data can be integrated and compared for system-wide analysis. Dr. Spitzer recently joined UCSF as a Sandler Fellow. Spring-boarding from the analytical methods he has already developed, his lab will continue to advance their understanding of how the immune system coordinates its responses across the organism with an emphasis on tumor immunology. The lab combines methods in experimental immunology and cancer biology with computation to understand the modes in which the immune system can respond to tumors and to rationally initiate curative immune responses against cancer.
Spitzer Lab: http://spitzerlab.ucsf.edu/home
- Professor and Vice-Chair, Department of Anatomy
- Associate Director for Basic Science, UCSF Helen Diller Family Comprehensive Cancer Center
RESEARCH AREAS
The Werb Lab focuses on breast cancer and the environment, concentrating on puberty as the window of susceptibility for the past 12 years. They concentrate on the molecular mechanisms involved in extracellular matrix remodeling and inflammatory cell function in mammary development and breast cancer metastasis. They have developed and used a variety of new technologies and models ranging from molecular biology to genetically engineered mouse models and patient-derived xenografts to intravital microscopy and 3D culture models. Their major interest is in driving the field of the extracellular microenvironment in development, inflammation, fibrosis, and tumor biology forward technically and conceptually, as well as determining insights from mammary development that help explain breast stem cells, and susceptibility to cancer development and metastasis.
Werb Lab: http://werblab.ucsf.edu
- Associate Professor, Department of Microbiology and Immunology
RESEARCH AREAS
In the Roybal Lab, we harness the tools of synthetic and chemical biology to enhance the therapeutic potential of engineered immune cells for cancer. We take a comprehensive approach to cellular engineering by developing new synthetic receptors, signal transduction cascades, and cellular response programs to enhance the safety and effectiveness of adoptive cell therapies. We also study the logic of natural cellular signaling systems, and the underlying principles of cellular communication and collective cell behavior during an immune response. These interests are complimentary as cell engineering is often informed by knowledge obtained from studying natural mechanisms of cell regulation refined by evolution.
Roybal Lab: https://www.roybal-lab.org