Salk Institute
NCI Cancer Center
Cancer Center Faculty

METABOLISM AND CANCER

The scientific goals of the Metabolism and Cancer Program are to study the intersection between metabolism and cancer, which has emerged as an important axis, with therapeutic relevance. The efforts include investigation of the LKB1-AMPK-mTOR pathway, which regulates cell growth and autophagy, transcriptional regulation downstream of the insulin receptor, and nuclear receptors that regulate metabolism. Pathways involved in circadian rhythms of gene expression and metabolism in different organs in the mouse, and the intersection between regulatory T cells and metabolism are being investigated. The role of inflammatory responses and the innate immune system in cancer are also areas of great interest, particularly in pancreatic cancer and non-small cell lung cancer. An effort in biosynthetic chemistry and natural products to develop small molecules that could lead to novel cancer therapeutics is also part of the program.

The program includes eight members from five different Salk Laboratories:

Ron Evans (Program Leader)
Area of interest: nuclear receptor function in metabolism and cancer
Disease models: pancreatic cancer, colon cancer, diabetes
Website: http://www.salk.edu/faculty/evans.html

Janelle Ayres
Area of interest: inflammation and pathobionts in the gut microbiota
Disease models: pathobionts, colorectal cancer
Website: http://www.salk.edu/faculty/ayres.html

Tony Hunter (Cancer Center Director)
Area of interest: phosphorylation, ubiquitylation and sumoylation in cancer
Disease models: cancer kinome, pancreatic cancer, glioblastoma, prostate cancer
Website: http://www.salk.edu/faculty/hunter.html

Marc Montminy
Area of interest: CRTC family transcriptional coactivators and glucose homeostasis
Disease models: insulin signaling and cancer, diabetes
Website: http://www.salk.edu/faculty/montminy.html

Joe Noel
Area of interest: biosynthetic enzyme engineering
Disease models: anti-cancer agents
Website: http://www.salk.edu/faculty/noel.html

Satchin Panda
Area of interest: circadian rhythms and metabolism
Disease models: colon, endometrial, breast and liver cancer
Website: http://www.salk.edu/faculty/panda.html

Reuben Shaw (Associate Program Leader)
Area of interest: AMPK in cancer and metabolism
Disease models: sporadic lung cancers (squamous and adenocarcinoma)
Website: http://www.salk.edu/faculty/shaw.html

Ye Zheng
Area of interest: T cell subset function in cancer and metabolism
Disease model; autoimmune disease and cancer
Website: http://www.salk.edu/faculty/zheng.html

MOUSE MODELS AND CANCER STEM CELLS

The scientific goals and central themes of the Mouse Models and Cancer Stem Cells Program are to investigate different aspects of stem cell function, including self renewal, reprogramming, and dedifferentiation and differentiation, using mouse, Drosophila, Xenopus, and zebrafish as models, with the goal of learning more about embryonic, tissue and cancer stem cells. Linked to this are major efforts to use induced pluripotent stem cell (iPSC) technology to study mechanisms of genomic reprogramming, including changes in DNA methylation patterns, to learn how cancer stem cells might arise through genomic reprogramming, and to develop "disease-in-a dish" models of human diseases. Developmental signaling pathways that are often reactivated and used to drive cancer cell phenotypes are being studied, including the Wnt/β-catenin pathway, the ERBB2, RET, and TAM receptor tyrosine kinases, and TGF-β pathways. The development and use of mouse models to study cancer biology and the role of inflammation in carcinogenesis, and also utilization of lentivirus vectors for cancer therapy and for development of new cancer models are also important goals.

The program includes twelve members from eight different Salk Laboratories

Inder Verma (Program Leader)
Area of interest: mouse models of cancer and lentivirus vector development
Disease models: inflammation, breast, prostate and ovarian cancer, glioblastoma
Website: http://www.salk.edu/faculty/verma.html

Senyon Choe
Area of interest: TGFβ receptor structure and signaling
Disease models: therapeutic modalities for the treatment of breast and liver cancer
Website: http://www.salk.edu/faculty/choe.html

Joe Ecker
Area of interest: epigenomics of stem cells and cancer cells
Disease models: breast cancer
Website: http://www.salk.edu/faculty/ecker.html

Fred Gage
Area of interest: stem cell self renewal and mobile elements in the nervous system and cancer
Disease models: ataxia telangiectasia, neurodegenerative disease
Website: http://www.salk.edu/faculty/gage.html

Juan Carlos Izpisua Belmonte
Area of interest: mechanisms underlying stem cell biology in cancer and regeneration
Disease models: genetic aberrations common to iPSCs that correlate with cancer genomic alterations
Website: http://www.salk.edu/faculty/belmonte.html

Chris Kintner
Area of interest: genetic pathways that drive multiciliate cell formation
Disease models: centriole assembly dysregulation and chromosomal instability in tumor cells
Website: http://www.salk.edu/faculty/kintner.html

Julie Law
Area of interest: epigenetic gene regulation and chromatin binding proteins
Disease model:
Website: http://www.salk.edu/faculty/law.html

Kuo-Fen Lee
Area of interest: integration of RTK and GPCR signaling pathways during mammalian development
Disease models: prostate, breast and non-small cell lung cancers
Website: http://www.salk.edu/faculty/lee.html

Greg Lemke
Area of interest: TAM receptor tyrosine kinase signaling in the immune system
Disease models: myeloid leukemia, metastatic lung cancer, renal cell carcinoma, prostatic carcinoma, breast cancer, and gastric cancer
Website: http://www.salk.edu/faculty/lemke.html

Axel Nimmerjahn
Area of interest: imaging tools to study glial cell dynamics in the live brain, and in glioblastomas
Disease models: glioblastoma
Website: http://www.salk.edu/faculty/nimmerjahn.html

Samuel Pfaff
Area of interest: signaling principles that control specification/connectivity of spinal neurons in locomotion
Disease models: post-polio syndrome
Website: http://www.salk.edu/faculty/pfaff.html

John Thomas
Area of interest: Drosophila glioblastoma model
Disease model: glioblastoma
Website: http://www.salk.edu/faculty/thomas.html

John Young
Area of interest: host cell factors in HIV infection
Disease model: cancer therapeutics, cancers caused by human retroviruses
Website: http://www.salk.edu/faculty/young.html

GROWTH CONTROL AND GENOMIC STABILITY

The overall scientific goal of the Growth Control and Genomic Stability Program is to understand mechanisms of proliferation, transcriptional regulation of oncogenic signaling pathways, DNA damage response and checkpoint activation, maintenance of genomic integrity and telomere function, and how these processes are disrupted or altered in cancer cells. Genomic instability is one of the key contributors to cancer progression and the genesis of tumor heterogeneity, and can engender either sensitivity or resistance to targeted and clastogenic cancer therapies. The members of this program study diverse aspects of how normal somatic cells, stem cells, and cancer cells respond to DNA damage, maintain genomic integrity, and respond to traditional and targeted chemotherapies. The functions of p53 in cell cycle checkpoint control and in diverse stress responses, and the use of adenovirus early proteins to interrogate cell signaling pathways and p53 checkpoint signaling comprise areas of significant focus of the program with opportunities for clinical translation. Chemical genetics is being used to study cellular signaling pathways that drive cancer cell proliferation. Other important topics include molecular mechanisms of transcriptional regulation of oncogenic pathways and of tumor suppressor gene expression, how nuclear pore subunits regulate gene expression, and the relationship of fetal mammary stem cells to stem-like cells in breast cancer.

The program includes nine members from five different Salk Laboratories:

Geoff Wahl (Program Leader)
Area of interest: p53 regulation, normal stem cells and stem-like cells in breast cancer, tumor heterogeneity
Disease models: breast cancer
Website: http://www.salk.edu/faculty/wahl.html

Beverly Emerson
Area of interest: transcriptional regulation of tumor suppressor genes
Disease models: breast cancer
Website: http://www.salk.edu/faculty/emerson.html

Martin Hetzer
Area of interest: nuclear pore protein function, micronuclei and cancer
Disease models: AML
Website: http://www.salk.edu/faculty/hetzer.html

Katherine Jones
Area of interest: Wnt/β-catenin signaling pathways and transcriptional regulation
Disease models: colon cancer
Website: http://www.salk.edu/faculty/jones.html

Jan Karlseder
Area of interest: telomere function and dysregulation in cancer cells
Disease models: combined treatment of cancer with mitotic inhibitors (Taxol, Velcade and Vinblastine) and PARP inhibitors
Website: http://www.salk.edu/faculty/karlseder.html

Björn Lillemeier
Area of interest: T cell receptor signaling mechanisms
Disease models: with immune cell cancers, including chronic lymphocytic leukemia
Website: http://www.salk.edu/faculty/lillemeier.html

Vicki Lundblad
Area of interest: telomeres and telomerase regulation in yeast
Disease models: therapeutic targets for telomerase inhibition in cancer
Website: http://www.salk.edu/faculty/lundblad.html

Clodagh O'Shea
Area of interest: oncolytic adenoviruses, adenovirus genome engineering and E4-ORF3 function
Disease models: tumor-selective oncolytic viral therapy
Website: http://www.salk.edu/faculty/oshea.html

Lei Wang
Area of interest: unnatural amino acid incorporation in tumor cells and stem cells
Disease models:
Website: http://www.salk.edu/faculty/wang.html


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