School of Medicine
Showing 11-20 of 28 Results
-
Justin Du Bois
Henry Dreyfus Professor of Chemistry and Professor, by courtesy, of Chemical and Systems Biology
BioThe Du Bois lab is heavily invested in exploring voltage-gated ion channel function and physiology and the underlying role of specific channels in human pathologies, particularly nociception, epilepsy, and neurodevelopmental disorders. With expertise in chemical synthesis, we have access to a collection of exceptional natural products—tetrodotoxin, saxitoxin, gonyautoxin, batrachotoxin, veratridine, antillatoxin, to name a few—that act as selective modulators of sodium ion channels (NaVs). In addition, we have developed novel molecules as inhibitors and agonists of specific voltage-gated chloride (ClCs) and calcium (CaVs) channel isoforms. As a lab, we are uniquely positioned to advance high-precision chemical tools to interrogate underlying biochemical mechanisms of electrogenesis. Our work in this arena is guided by a number of questions related to the basic functioning of voltage-gated channels in neuronal cells and glia that include: 1) what is the rate at which channels are being made and degraded and is the rate of channel turnover context dependent (i.e., is protein turnover affected by increased neuronal activity, nerve cell damage, etc.); 2) to what extent is channel expression and cellular distribution affected by external factors (pH, inflammatory modulators, injury); 3) how do post-translational protein modifications influence channel function and how are such modifications altered in response to external factors; 4) how do neighboring glia influence channel expression and ion gating. Answers to these types of questions will provide a deeper understanding of the molecular mechanisms by which neuronal cells and tissue respond to external stimuli, stress, and injury. We benefit from the strong interest of others in our work and multiple collaborators at Stanford and at other institutions.
Ion channel function and physiology. We wish to understand the role of individual subtypes of voltage-gated sodium, chloride, and calcium channels in neuronal signaling and how structural changes (i.e., point mutations, post-translational modifications, partner proteins) alter channel function. Our interests include the design, development, and application of chemogenetic technologies for targeting individual channel subtypes and allosteric modulators of select channel isoforms. Our work aims to inform efforts in translational research, as voltage-gated ion channel dysregulation and malfunction underlie a wide range of human diseases and disorders.
Natural products synthesis. We are interested in developing efficient and flexible synthetic routes to natural products that serve as ‘lead’ compounds for advancing high precision pharmacological tools. Most of the targets we are interested in obtaining are not available in sufficient quantities from natural sources, thus necessitating de novo preparation. To streamline the assembly process of these complex molecules, we are challenged to develop, in parallel, new tactics and chemical methods that facilitate C–C, C–N, and C–O bond formation.
Toxin ‘sponge’ proteins. A longstanding collaboration with the Minor lab at UCSF has focused on understanding how certain organisms that ingest dietary toxins such as saxitoxin, tetrodotoxin, and batrachotoxin survive their poisonous effects. This work has resulted in the elucidation of the structures of novel paralytic shellfish-binding proteins (so-called saxiphilins) and the toxin ‘binding code’. Studies are ongoing to integrate saxiphilins into a diagnostic device for measuring toxin concentrations in shellfish and to advance an engineered toxin-binding protein as a countermeasure for paralytic shellfish poisoning. -
James Ferrell
Professor of Chemical and Systems Biology and of Biochemistry
Current Research and Scholarly InterestsMy lab has two main goals: to understand the regulation of mitosis and to understand the systems-level logic of simple signaling circuits. We often make use of Xenopus laevis oocytes, eggs, and cell-free extracts for both sorts of study. We also carry out single-cell fluorescence imaging studies on mammalian cell lines. Our experimental work is complemented by computational and theoretical studies aimed at understanding the design principles and recurring themes of regulatory circuits.
-
Nathanael S. Gray
Krishnan-Shah Family Professor
BioNathanael Gray is the Krishnan-Shah Family Professor of Chemical and Systems Biology at Stanford, Co-Director of Cancer Drug Discovery Co-Leader of the Cancer Therapeutics Research Program, Member of Chem-H, and Program Leader for Small Molecule Drug Discovery for the Innovative Medicines Accelerator (IMA). His research utilizes the tools of synthetic chemistry, protein biochemistry, and cancer biology to discover and validate new strategies for the inhibition of anti-cancer targets. Dr. Gray’s research has had broad impact in the areas of kinase inhibitor design and in circumventing drug resistance.
Dr. Gray received his PhD in organic chemistry from the University of California at Berkeley in 1999 after receiving his BS degree with the highest honor award from the same institution in 1995. After completing his PhD, Dr. Gray was recruited to the newly established Genomics Institute of the Novartis Research Foundation (GNF) in San Diego, California. During his six year stay at GNF, Dr. Gray became the director of biological chemistry where he supervised a group of over fifty researchers integrating chemical, biological and pharmacological approaches towards the development of new experimental drugs. Some of the notable accomplishments of Dr. Gray’s team at GNF include: discovery of the first allosteric inhibitors of wild-type and mutant forms of BCR-ABL which resulted in clinical development of ABL001; discovery of the first selective inhibitors of the Anaplastic Lymphoma Kinase (ALK), an achievement that led to the development of now FDA-approved drugs such as ceritinib (LDK378) for the treatment of EML4-ALK expressing non-small cell lung cancer (NSCLC); and discovery that sphingosine-1-phosphate receptor-1 (S1P1) is the pharmacologically relevant target of the immunosuppressant drug Fingomilod (FTY720) followed by the development of Siponimod (BAF312), which is currently used for the treatment of multiple sclerosis.
In 2006, Dr. Gray returned to academia as a faculty member at the Dana Farber Cancer Institute and Harvard Medical School in Boston. There, he has established a discovery chemistry group that focuses on developing first-in-class inhibitors for newly emerging biological targets, including resistant alleles of existing targets, as well as inhibitors of well-validated targets, such as Her3 and RAS, that have previously been considered recalcitrant to small molecule drug development. Dr. Gray’s team developed covalent inhibitors of the T790M mutant of EGFR inspired the development of Osimertinib (AZD9291), now FDA approved for treatment of patients with relapsed lung cancer due to resistance to first generation EGFR inhibitors. Dr. Gray has also developed structure-based, generalized approaches for designing drugs to overcome one of the most common mechanisms of resistance observed against most kinase inhibitor drugs, mutation of the so-called "gatekeeper" residue, which has been observed in resistance to drugs targeting BCR-ABL, c-KIT and PDGFR.
In 2021, Dr. Gray joined Stanford University where he has joined the Stanford Cancer Institute, Chem-H and the Innovative Medicines Accelerator (IMA) to spur the development of prototype drugs.
These contributions have been recognized through numerous awards including the National Science Foundation’s Career award in 2007, the Damon Runyon Foundation Innovator award in 2008, the American Association for Cancer Research for Team Science in 2010 and for Outstanding Achievement in 2011 and the American Chemical Society award for Biological Chemistry in 2011, and the Nancy Lurie Marks endowed professorship in 2015 and the Paul Marks Prize in 2019, and the Hope Funds for Cancer Research in 2023. -
Daniel Jarosz
Senior Associate Dean, Basic Science, Professor of Chemical and Systems Biology and of Developmental Biology
Current Research and Scholarly InterestsMy laboratory studies conformational switches in evolution, disease, and development. We focus on how molecular chaperones, proteins that help other biomolecules to fold, affect the phenotypic output of genetic variation. To do so we combine classical biochemistry and genetics with systems-level approaches. Ultimately we seek to understand how homeostatic mechanisms influence the acquisition of biological novelty and identify means of manipulating them for therapeutic and biosynthetic benefit.
-
Michael Lin
Professor of Neurobiology, of Bioengineering and, by courtesy, of Chemical and Systems Biology
Current Research and Scholarly InterestsMy interests are in novel technologies to investigate in vivo biology and improve molecular medicines. These include the use of viral proteases and protease inhibitors to control protein function in vivo, the invention of cofactor-independent photoswitchable proteins for investigating signaling dynamics and controlling gene editing in vivo, the development of fully genetically encoded voltage indicators, and a new approach of treating cancer by rewiring oncogenic pathways to cell ablation.
-
Nicole M. Martinez
Assistant Professor of Chemical and Systems Biology and of Developmental Biology
Current Research and Scholarly InterestsThe Martinez lab studies RNA regulatory mechanisms that control gene expression. We focus on mRNA processing, RNA modifications and their roles in development and disease.
-
Mark Mercola
Professor of Medicine (Cardiovascular) and, by courtesy, of Chemical and Systems Biology
BioDr. Mercola is Professor of Medicine and Professor in the Stanford Cardiovascular Institute. He completed postdoctoral training at the Dana-Farber Cancer Institute and Harvard Medical School, was on the faculty in the Department of Cell Biology at Harvard Medical School for 12 years, and later at the Sanford-Burnham-Prebys Institute and Department of Bioengineering at the University of California, San Diego before relocating to Stanford in 2015.
Prof. Mercola is known for identifying many of the factors that are responsible for inducing and forming the heart, including the discovery that Wnt inhibition is a critical step in cardiogenesis that provided the conceptual basis and reagents for the large-scale production of cardiovascular tissues from pluripotent stem cells. He has collaborated with medicinal chemists, optical engineers and software developers to pioneer the use of patient iPSC-cardiomyocytes for disease modeling, safety pharmacology and drug development. His academic research is focused on developing and using quantitative high throughput assays of patient-specific cardiomyocyte function to discover druggable targets for preserving contractile function in heart failure and promoting regeneration following ischemic injury. He co-established drug screening and assay development at the Conrad Prebys Drug Discovery Center (San Diego), which operated as one of 4 large screening centers of the US National Institutes of Health (NIH) Molecular Libraries screening initiative and continues as one of the largest academic drug screening centers.
Prof. Mercola received an NIH MERIT award for his work on heart formation. He holds numerous patents, including describing the invention of the first engineered dominant negative protein and small molecules for stem cell and cancer applications. He serves on multiple editorial and advisory boards, including Vala Sciences, Regencor, The Ted Rogers Centre for Heart Research and the Human Biomolecular Research Institute. His laboratory is funded by the National Institutes of Health (NIH), California Institute for Regenerative Medicine, Phospholamban Foundation and Fondation Leducq. -
Daria Mochly-Rosen
George D. Smith Professor of Translational Medicine
Current Research and Scholarly InterestsTwo areas: 1. Using rationally-designed peptide inhibitors to study protein-protein interactions in cell signaling. Focus: protein kinase C in heart and large GTPases regulating mitochondrial dynamics in neurodegdenration. 2. Using small molecules (identified in a high throughput screens and synthetic chemistry) as activators and inhibitors of aldehyde dehydrogenases, a family of detoxifying enzymes, and glucose-6-phoshate dehydrogenase, in normal cells and in models of human diseases.
-
Kacper Rogala
Assistant Professor of Structural Biology and of Chemical and Systems Biology
Current Research and Scholarly InterestsOur team is fascinated by how cells make growth decisions — to grow or not to grow. In order to grow, cells require nutrients, and we are unraveling how cells use specialized protein sensors and transporters to sense and traffic nutrients in between various compartments. We use approaches from structural biology, chemical biology, biophysics, biochemistry, and cell biology — to reveal the mechanisms of basic biological processes, and we develop chemical probes that modulate them.
