School of Medicine
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Professor of Medicine (Hematology) and of Biochemistry
Current Research and Scholarly Interests Telomeres are nucleoprotein complexes that protect chromosome ends and shorten with cell division and aging. We are interested in how telomere shortening influences cancer, stem cell function, aging and human disease. Telomerase is a reverse transcriptase that synthesizes telomere repeats and is expressed in stem cells and in cancer. We have found that telomerase also regulates stem cells and we are pursuing the function of telomerase through diverse genetic and biochemical approaches.
Professor of Biochemistry, Emeritus
Current Research and Scholarly Interests I closed my laboratory when I retired in 1998. I continue to do research, chiefly in collaboration with Franc Avbelj, on problems of protein folding energetics, especially peptide backbone solvation, and to write reviews.
The Ernest and Amelia Gallo Professor in the School of Medicine and Professor of Developmental Biology
Current Research and Scholarly Interests Function of Hedgehog proteins and other extracellular signals in morphogenesis (pattern formation), in injury repair and regeneration (pattern maintenance). We study how the distribution of such signals is regulated in tissues, how cells perceive and respond to distinct concentrations of signals, and how such signaling pathways arose in evolution. We also study the normal roles of such signals in stem-cell physiology and their abnormal roles in the formation and expansion of cancer stem cells.
Postdoctoral Research fellow, Biochemistry
Bio During my PhD work with Stephen Kowalczykowski at UC Davis, I studied homologous recombination and DNA repair, which can be applied towards (but not limited to) cancer biology and gene therapy. Homologous recombination is a complex and highly conserved process that involves the sequential processing of various DNA substrates by dozens of proteins. In humans, the recombination pathway is intimately entangled with DNA replication, the DNA damage response, DNA repair, cell cycle control, apoptosis and telomere maintenance. All of these pathways are implicated in cancer biology. Specifically, my dissertation focused on the regulated assembly of RecA on single molecules of SSB-coated ssDNA.
I remained at UC Davis for a short postdoc, where I used single-molecule biophysics to visualize and characterize the biochemical activities of the yeast helicase, Sgs1, which is the homologue of the human BLM protein. Genetic defects in BLM are associated with an anomalously high predisposition for developing sporadic cancers due to genomic instability caused by defects in DNA repair and homologous recombination pathways. I am particularly interested in how the biochemical activity of Sgs1 is regulated during DNA double strand break repair by accessory proteins, including Top3, Rmi1, RPA, Rad51, Mre11 and Xrs2. In addition to my work on Sgs1, I am also collaborating with several scientists in our group to study the molecular mechanism of BRCA2 during homologous recombination-mediated DNA repair using "visual biochemical" techniques.
I have joined Aaron Straight's lab in the Department of Biochemistry in order to study the spatio-temporal assembly of the centromere and kinetochore with single-molecule resolution.
Emeritus Faculty, Acad Council, Biochemistry
Current Research and Scholarly Interests For about 10 years until 2000, my lab's research activities were focused on the mechanism of recombinational repair of double-strand breaks in DNA. We focused our efforts on two model systems: one involved the repair of restriction enzyme cleavages at specific mammalian chromosomal loci and the second explored the biochemical properties of purified yeast Rad51 protein, an essential catalyst for synapsing the broken ends of DNA with an intact homologue of that sequence. We also explored the roles of Rad52 and PRA (single-strand DNA binding protein) in the repair process.
In 2000, I became Emeritus Professor in Biochemistry and stepped down from the Directorship of the Beckman Center. Much of my activities since then have been involved in writing a biography of the genetics pioneer George Beadle, published in 2003, plus articles for other publications elaborating on Beadle's legacy for today's science. Over the years I have been and continue to be an activist in public policy issues affecting biomedical issues, e.g. recombinant DNA and more recently, issues concerning embryonic stem cells.
Assistant Professor of Biochemistry
Current Research and Scholarly Interests The Brandman Lab studies how cells ensure protein quality and how they signal stress. To achieve this, we employ an integrated set of techniques including single cell anaysis of stress pathways, structural studies, in vitro translation, and full genome screens in yeast and mammalian cells.
Patrick O. Brown
Professor of Biochemistry
Current Research and Scholarly Interests Dr. Brown's research group uses diverse experimental and computational methods to investigate the logic and mechanisms that control a genome's expression program. The Brown laboratory is systematically characterizing the genetic scripts that control the expression of our genes, in normal development and physiology and in diseases like cancer, with a particular focus on post-transcriptional regulation. The Brown lab also develops strategies and assays for early detection and diagnosis of cancer.