John C. Reed, M.D., Ph.D.[La Jolla]
Multidisciplinary collaborations are a core component of our strategy at Sanford-Burnham. Through collaboration, the discoveries we make in the laboratory can more quickly be translated into improved healthcare outcomes for patients.
Dr. Reed has made seminal contributions to the understanding of fundamental mechanisms of cell life-span regulation in health and disease.
Dr. Reed is author of over 850 research publications. He heads pharma research and early development for Roche.
XIAP mediates NOD signaling via interaction with RIP2.
Krieg A, Correa RG, Garrison JB, Le Negrate G, Welsh K, Huang Z, Knoefel WT, Reed JC
Proc Natl Acad Sci U S A. 2009 Aug 25;106(34):14524-9
Bcl-2 family proteins and cancer.
Yip KW, Reed JC
Oncogene. 2008 Oct 27;27(50):6398-406
Daxx represses RelB target promoters via DNA methyltransferase recruitment and DNA hypermethylation.
Puto LA, Reed JC
Genes Dev. 2008 Apr 15;22(8):998-1010
Bcl-2-family proteins and hematologic malignancies: history and future prospects.
Blood. 2008 Apr 1;111(7):3322-30
Bcl-2 and Bcl-XL regulate proinflammatory caspase-1 activation by interaction with NALP1.
Bruey JM, Bruey-Sedano N, Luciano F, Zhai D, Balpai R, Xu C, Kress CL, Bailly-Maitre B, Li X, Osterman A, Matsuzawa S, Terskikh AV, Faustin B, Reed JC
Cell. 2007 Apr 6;129(1):45-56
Reconstituted NALP1 inflammasome reveals two-step mechanism of caspase-1 activation.
Faustin B, Lartigue L, Bruey JM, Luciano F, Sergienko E, Bailly-Maitre B, Volkmann N, Hanein D, Rouiller I, Reed JC
Mol Cell. 2007 Mar 9;25(5):713-24
Drug insight: cancer therapy strategies based on restoration of endogenous cell death mechanisms.
Nat Clin Pract Oncol. 2006 Jul;3(7):388-98
Proapoptotic multidomain Bcl-2/Bax-family proteins: mechanisms, physiological roles, and therapeutic opportunities.
Cell Death Differ. 2006 Aug;13(8):1378-86
Apoptosis-based therapies for hematologic malignancies.
Reed JC, Pellecchia M
Blood. 2005 Jul 15;106(2):408-18
BI-1 regulates an apoptosis pathway linked to endoplasmic reticulum stress.
Chae HJ, Kim HR, Xu C, Bailly-Maitre B, Krajewska M, Krajewski S, Banares S, Cui J, Digicaylioglu M, Ke N, Kitada S, Monosov E, Thomas M, Kress CL, Babendure JR, Tsien RY, Lipton SA, Reed JC
Mol Cell. 2004 Aug 13;15(3):355-66
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Orphan Nuclear Receptor NR4A1 binds a novel protein interaction site on anti-apoptotic B-cell lymphoma gene-2 family proteins.
Godoi PH, Wilkie-Grantham RP, Hishiki A, Sano R, Matsuzawa Y, Yanagi H, Munte CE, Chen Y, Yao Y, Marassi FM, Kalbitzer HR, Matsuzawa SI, Reed JC
J Biol Chem. 2016 Apr 19;
John C. Reed's Research Focus
Cancer, Inflammatory/Autoimmune Disease, Neurological (Brain) Diseases, Traumatic Injury
Watch Dr. Reed discuss his research
Dr. Reed’s laboratory studies the fundamental mechanisms that regulate cell lifespan. His team analyzes how those mechanisms go awry in disease states. They are interested in how the defective regulation of programmed cell death results in diseases such as Alzheimer’s (when too much cell death occurs) and cancer (when too little cell death takes place). The Reed laboratory also studies the intersection of cell death with infections and inflammatory diseases.
John C. Reed's Research Report
Apoptosis and Cell Death
Cell death is a natural part of life. Every day in the human body, 50-70 billion cells die, making room for the equivalent number of new cells produced daily through cell division. So massive is the flux of cell birth and death in our bodies, that in the course of single year, each of us will produce and in parallel eradicate a mass of cells equal to our entire body weight.
Our cells are endowed with a suicide mechanism that instructs
cells when it is time to die. Unfortunately, defects in the
regulation of this cell suicide program can occur, leading to
diseases characterized by either too much cell death [cell loss]
(stroke; heart failure; Alzheimer’s; Parkinson’s; AIDS) or too
little cell death [cell accumulation] (cancer; auto-immunity). In fact, it is estimated that over half of the major medical illnesses for which effective treatments or preventions are currently lacking can be attributed directly or indirectly to defective regulation of programmed cell death mechanisms.
Our laboratory studies fundamental mechanisms of cell life-span regulation, and analyzes how those mechanisms go awry in disease states. We use tools of genomics, proteomics,
metabolomics, chemical biology, and bioinformatics to discover genes involved in the causation or suppression of cell death. Characterization of the molecular mechanisms by which the proteins encoded by those genes control cell life and death then provides insights that set the stage for drug discovery. Advances from our laboratory have thus far resulted in a new
candidate therapies for cancer, which are in clinical trials, and numerous drug-discovery programs at earlier stages of development for cancer, stroke, inflammation, and auto-immunity. Discoveries from our laboratory have also revealed potential new diagnostic tests that can predict whether cancer patients will or will not relapse after receiving therapy, thus providing much need information in planning optimal medical management.
Programmed Cell Death in Malignancy
Defects in the regulation of apoptosis (programmed cell death) make important contributions to the pathogenesis or severity of many diseases, including cancer, autoimmunity, inflammation, neurodegeneration, and ischemic diseases (heart attack; stroke). Indeed, it is estimated that over half of the major medical illnesses for which effective treatments or preventions are currently lacking can be attributed directly or indirectly to defective regulation of programmed cell death mechanisms.
Apoptosis is caused by activation of intracellular proteases, known as "caspases," which are responsible directly or indirectly for the morphological and biochemical events that characterize the apoptotic cell. Numerous proteins that regulate these cell death proteases have been discovered, including proteins belonging to the Bcl-2, IAP, CARD, Death Domain (DD), Death Effector Domain (DED) families. These caspase-regulating proteins provide mechanisms for linking environmental stimuli to cell death responses (e.g. DNA damage, microtubule disruption; cytokine stimulation) or to maintenance of cell survival (e.g., growth factors; cell adhesion receptors; oncoproteins). Knowledge of the molecular details of apoptosis regulation and the 3-dimensional structures of apoptosis proteins have revealed new strategies for identifying small-molecule drugs that may one day yield more effective treatments for several diseases. Apoptosis-regulating genes are also beginning to find utility as targets for antisense oligonucleotides or for use in gene therapy applications. Moreover, knowledge about the signal transduction pathways that control the expression of apoptosis gene or that modulate the functions of apoptosis-proteins can be exploited for altering the balance of pro- and anti-apoptotic gene expression and function, using protein kinase inhibitors, regulators of steroid/retinoid-family transcription factors, and other approaches.
Our laboratory studies fundamental mechanisms of apoptotic and
non-apoptotic cell death regulation, and analyzes how those mechanisms go awry in disease states. The experimental approaches employed include genomics, proteomics, bioinformatics, structural biology, and chemistry. Some of the discoveries made by the laboratory include (a) establishing the role of Bcl-2 in cancer chemoresistance and use of antisense methods to reduce Bcl-2 expression for sensitizing tumor cells to anti-cancer drugs (a
concept tested in clinical trials); (b) demonstration of a critical role for mitochondria in apoptosis mechanisms using a cell-free system; (c) discovery that p53 induces transcription of death-gene Bax, representing the first p53–inducible pro-apoptotic gene; (d) discovery of the mechanism of IAP-family proteins, as endogenous suppressors of Caspase-family proteases; (e) discovery of BAG-family proteins and their role in cellular stress resistance; and (f) development of prognostic biomarkers that predict clinical outcome in patients with cancer.
Dr. Reed has been engaged in research on immunity, inflammation and infectious diseases for nearly 25 years. He obtained his doctoral degree in Immunology in 1986, initially studying signaling mechanisms of lymphokine receptors, then progressing to investigations of cytopathic mechanisms of Human Immunodeficiency Virus (HIV) and other topics in immunobiology. Dr. Reed’s current interests focus on innate immunity, including studies of NLR-family proteins (intracellular analogs of the Toll-Like Receptors [TLRs], PYRIN domain (PYD)-containing proteins, and the role of TRAF-family adapter proteins in signaling by members of the Tumor Necrosis Factor (TNF) Receptor family. Dr. Reed is the co-discoverer of several NLR-family proteins, several PYD-containing proteins, TRAF3, and several proteins involved in regulation of pro-inflammatory Caspase-family proteases and NF-κB. The Reed laboratory is also engaged in research on pathogens, with a focus on virulence factors encoded in the genomes of bacterial and viruses that impinge on signaling transduction pathways regulating inflammatory Caspases, NF-κB, and apoptosis in infected host cells. Translational applications of the basic discovery research conducted in the Reed laboratory include high throughput screens for novel immunoadjuvants that stimulate NLR-family proteins, and chemical inhibitors of NLRs and TRAF-associated proteins with potential utility for treatment of inflammatory and autoimmune diseases, sepsis, and other conditions.
About John C. Reed
John C. Reed, M.D., Ph.D. is head of Pharma Research and Early Development at Roche, the world's largest biotechnology company.
Dr. Reed is one of the world’s leading biomedical researchers. He has authored more than 850 medical research publications. The Institute for Scientific Information recognized Dr. Reed as the world’s most highly cited scientist from 1995 to 2005 in the fields of cell biology and general biomedicine. At the same time, Thomson Scientific named him “Doctor of the Decade.” Dr. Reed is the recipient of over one-hundred competitive research grants, an inventor on more than 90 patents, and the founder or co-founder of several biotechnology companies. He has led various national research initiatives, has served on numerous editorial and advisory boards, and has served as a director of several biopharmaceutical companies. In 2011, he was elected fellow of the American Association for the Advancement of Science.
Under Dr. Reed’s leadership, Sanford-Burnham has risen to become one of the world’s top laboratory-based medical research institutes. The Institute combines outstanding discovery research with advanced capabilities in innovative therapeutics development to translate breakthroughs in understanding disease mechanisms into promising experimental therapeutics. Advances from Dr. Reed’s laboratory have spawned several drug discovery and development programs for cancer, neuroprotection, autoimmunity, and other diseases.
• Resident in Clinical Pathology, Hospital of the University of Pennsylvania, 1986-1989
• Postdoctoral Fellow in Molecular Biology, Wistar Institute of Anatomy and Biology
• M.D., Ph.D., University of Pennsylvania, School of Medicine, 1986
• B.A., University of Virginia, 1980
• Adjunct Professor, Department of Biochemistry, University of Florida
• Adjunct Professor, School of Medicine, University of Central Florida
• Associate Member, Whitaker Institute of Biomedical Engineering, University of California, San Diego
• Adjunct Professor, Department of Molecular Pathology, University of California, San Diego School of Medicine
• Adjunct Professor, Department of Biology, San Diego State University
Honors and Recognition
• BIOCOM Life Sciences Heritage Award, 2008
• Danny Thomas Lecture Series, St. Jude Children’s Research Hospital, 2007
• Donald Ware Waddell Award, 2007
• Achievement Rewards for College Scientists, Scientist of the Year Award, San Diego Chapter, 2007
• Thomson Scientific – Doctors of the decade, 1995-2005