UCSF Sandler Fellows:
Joseph Bondy-Denomy, Ph.D. Joe conducted his Ph.D. training at the University of Toronto where he was a graduate student with Alan Davidson in the Department of Molecular Genetics. The primary goal of his research was understanding the co-evolutionary arms race between bacterial viruses (phages) and their hosts. This work led Joe to study an immune system that bacteria possess to protect them from phages, called CRISPR-Cas. He discovered numerous phage-encoded proteins that inhibit CRISPR-Cas function and characterized their mechanisms of action. As a Fellow at UCSF, Joe will continue to study various aspects of the CRISPR-Cas system, such as characterizing its roles in other pathogenic microbes and searching for proteins that may modulate or redirect CRISPR-Cas function. Joe is also interested in discovering novel bacterial immune systems, using phages to probe for them. His laboratory will use a combination of molecular, microbiological and bioinformatic approaches to identify and characterize novel aspects of bacterial immune systems. Joe’s work will enhance our understanding of bacterial evolution, has potential applications to CRISPR-Cas9 genome editing, and may provide novel therapeutic targets for antibiotic resistant bacteria.
Faranak Fattahi, Ph.D. Faranak completed her graduate training in the laboratory of Dr. Lorenz Studer at Memorial Sloan-Kettering Cancer Center. During her PhD, she pioneered strategies to derive highly specific lineages of the peripheral nervous system (PNS) from human pluripotent stem cells and demonstrated their potential in drug discovery and regenerative medicine. As a UCSF Sandler Fellow, she is focused on utilizing this unique framework to study the human PNS development and function in health and disease, with the ultimate goal of developing new therapies for peripheral neuropathies.
Robert Judson, Ph.D. Robert conducted his dissertation research in Robert Blelloch’s laboratory in the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF. There he pioneered the use of microRNAs for epigenetic reprogramming and discovered two conserved microRNA families that promote the conversion of differentiated cells into induced pluripotent stem cells. Using an siRNA approach to map genetic interactions, he further identified networks of microRNA-regulated genes that cooperate in the stabilization of the fibroblastic cell state. Coordinated inhibition of these networks sensitizes skin cells to epigenetic reprogramming, thereby making them more susceptible to the reacquisition of embryonic programs. As a fellow at the UCSF Helen Diller Family Comprehensive Cancer Center, Robert is now further developing these tools to dissect the similar networks that stabilize the melanocytic cell state. The incidence of melanoma is on the rise and, if given the opportunity to metastasize, the disease is usually lethal. With the goal of developing novel strategies to more accurately determine the metastatic potential of early lesions, Robert is using a combination of primary tumor sequencing, genetic interaction mapping, genome editing, and microRNA manipulation to study the networks of genes that prevent normal melanocytes and primary melanomas from reacquiring embryonic programs.
Melissa McCreery, Ph.D.Melissa did her graduate research in Allan Balmain's lab in the Helen Diller Comprehensive Cancer Center at UCSF, where she studied tumor evolution and heterogeneity. Combining next generation sequencing with multi-color fluorescent lineage tracing, she identified patterns of clonal evolution and timing of clonal sweeps that occur during tumor progression and found that metastases typically spread from the primary tumor in parallel to distant sites, rather than via a regional lymph node. As a UCSF Sandler Fellow, Melissa and her lab will study how tumor heterogeneity impacts the anti-tumor immune response, making use of multi-color lineage tracing tools and next-gen sequencing. Immunotherapy strategies have great potential to treat and even cure cancer patients, but the majority of human tumors exhibit a high level of spatial and genetic heterogeneity, and it is critical for us to understand how that heterogeneity will impact the response of T cells to the tumor.
Georgia Panagiotakos, Ph.D. Georgia has been a graduate student working with Ricardo Dolmetsch and Theo Palmer at the Stanford University School of Medicine and will be joining UCSF late in 2014. She is primarily interested in how immature, undifferentiated neural stem cells integrate a variety of intrinsic and extrinsic signals to generate the diverse array of cell types in the developing brain. Georgia first became passionate about neural development during her time working with Viviane Tabar and Lorenz Studer at Memorial Sloan Kettering Cancer Center, where she focused on the transplantation of pluripotent stem cells that had been directed to differentiate into specific neural cell types. This work shed light on the integration of stem cell-derived neural cells into the brain, in the context of developing strategies to replace cells lost during disease. For her graduate work at Stanford, Georgia continued to explore mechanisms by which neural stem cells decide to become a specific type of neuron, by investigating the role of a calcium channel implicated in neuropsychiatric disease on the differentiation of mouse and human neurons. To do this, she employed a number of different techniques, including in utero electroporation, genetic tools, single cell multiplex qPCR, ratiometric calcium imaging, and human induced pluripotent stem cell culture. As a UCSF Sandler Fellow, Georgia will integrate these complementary approaches to examine the function of early electrical activity and ion channel diversity in sculpting the development and evolution of the brain, with an eye towards understanding how these mechanisms go awry in neurodevelopmental disorders.
Sy Redding, Ph.D. Sy did his graduate work at Columbia University in the laboratories of Eric Greene and David Reichman. Using a single molecule imaging technique called DNA curtains, Sy investigated the physical mechanisms through which proteins locate, recognize, and extract genomic information. His research has explored how bacterial RNA polymerase locates promoter sequences within the genome, the mechanism of sequence alignment during homologous recombination, and how viruses are selectively recognized and destroyed by the CRISPR immune system. At UCSF, Sy will use DNA curtains to explore how protein-DNA interactions change as DNA is organized into chromatin: how nature balances the individual protein’s need to access DNA against the cell’s pressure to organize the genome.
Matthew Spitzer, Ph.D. Matt completed his training in Immunology at Stanford University in the laboratories of Garry Nolan and Edgar Engleman. There, he developed experimental and analytical methods to model the state of the immune system using high dimensional single-cell data. This led Matt to develop the first reference map of the immune system, providing a framework into which new data can be integrated and compared for system-wide analysis. At Stanford, he also developed new strategies for inducing powerful immune responses against cancer. As a UCSF Sandler Fellow, Matt will continue to develop our understanding of how the immune system coordinates its responses across the organism with an emphasis on tumor immunology. Matt’s 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.
David Weinberg, Ph.D. David was a graduate student with Dave Bartel at the Whitehead Institute at MIT and joined UCSF in 2013. While a student, he uncovered key RNAi pathway components and target genes in budding yeast. David also discovered how the Dicer processing enzyme uses an unusual mechanism and structure to act a molecular ruler, and how Argonaute utilizes guide RNAs in RISC complexes. While still at MIT, he initiated an independent program to study eukaryotic translation regulation, including the roles of cellular context, RNA sequence, and mRNA looping on translational efficiency, and the proteins involved, and is now investigating these aspects as a UCSF Sandler Fellow.
Kevin Yackle, M.D., Ph.D. Kevin completed his training at Stanford University where his dissertation in Mark Krasnow’s lab made a foundational contribution towards understanding the cellular and molecular bases of breathing rhythm generation. Breathing is a simple, essential behavior triggered roughly fifteen times per minute by the breathing pacemaker, the preBötzinger Complex (preBötC), a brainstem nucleus of several thousand neurons. Kevin defined more than 50 molecularly distinct preBötC neural subtypes and in initial studies characterizing the first five subtypes, he discovered that molecular defined preBötC cell types that have exquisitely specific, distinct and interesting functions in the breathing behavior. For example, he identified ~200 preBötC neurons that are sufficient to induce and selectively required for the control of sighing, a specific breath type, and ~175 different neurons that are expendable for breathing rhythm generation and instead project to, synapse with, and activate a higher order brain center that promotes arousal, perhaps explaining the connection between breathing and calmness or anxiety. The discovery of dozens of molecularly distinct preBötC neural cell types, each with an important and distinct role in breathing, suggests that a subset will be critical for generating a breath and controlling the pace of breathing. At UCSF, Kevin will continue his dissection of preBötC cell types in order to identify the key neural types and the molecules they use to generate and pace breathing.
Systems Biology Fellows:
The UCSF Center for Systems and Synthetic Biology has recruited additional Faculty Fellows. These independent research positions are similar to UCSF Sandler Fellows but are administered by a different committee.
Matt Thomson, Ph.D. Matt's graduate research at Harvard University focused on understanding how molecular circuits enable individual cells to make cell fate decisions in response to developmental signals. Currently, Matt is exploring cellular decisions that occur in cell populations, for example, within the tissues of a developing organism or within our immune system. How do large numbers of progenitor cells within a developing organism exchange information and coordinate their state to construct a complex tissue? What are the rules that organize multi-cellular phenomena and how are these rules implemented in molecular circuits that operate in single cells? He is using a combination of approaches including mathematical models, statistical analysis of high-throughput gene expression data, and single cell imaging experiments. His current work is reconstituting a set of developmental processes in the lab using embryonic stem cell differentiation and developing imaging methods for tracking and perturbing the activity of signaling pathways and transcriptional regulators in many single cells at once. Matt will use this data with computational models to classify mechanisms used by tissues to develop and repair themselves without centralized control.
The California Institute of Quantitative Biosciences (QB3) at UCSF has also recruited Faculty Fellows. These independent research positions are similar to UCSF Sandler Fellows but administered by a different committee.
Graham Johnson, Ph.D. Graham was a graduate student in the Molecular Graphic Lab at Scripps. He focuses primarily on developing algorithms to enable scientists to generate, simulate, and visualize molecular models of cells, namely a software called autoFill/autoCell and continues to work with Ludovic Autin to develop ePMV in continued collaboration with Arthur Olson's lab at Scripps. His lab also develops outreach software that enables scientists and illustrators to interoperate the computational tools of science and art and works closely on these fronts with Tom Ferrin's Computer Graphics Lab (CGL) at UCSF as a Resource for Biocomputing, and Visualization, and Informatics (RBVI) collaborator, and with the Molecular Graphics Lab (MGL) at The Scripps Research Institute as a former National Biomedical Computational Resource (NBCR) member and current collaborator.
Physician-Scientist Scholar Program:
The Physician-Scientist Scholar Program (PSSP) attracts the most accomplished and promising young physician/scientists to UCSF and accelerates their transition to independent laboratory-based investigators working on research problems relevant to human health. These are early-career Scholars, like UCSF Sandler Fellows, but are administered by a different committee.
Alexandra Nelson, M.D., Ph.D. Alexandra completed her joint MD and PhD training at University of California, San Diego. Her thesis work under the mentorship of Sascha du Lac at the Salk Institute employed whole-cell electrophysiology in rodents, and identified a novel form of neuronal excitability plasticity involving the regulation of potassium channels. She later found this form of plasticity contributes to motor learning in vivo. After completing her Neurology residency training at UCSF, she began postdoctoral work in the laboratory of Anatol Kreitzer at the Gladstone Institute. There she combined electrophysiology with optogenetics, in order to probe basal ganglia circuitry in mouse models. As a UCSF Physician-Scientist Scholar, Alexandra plans on using in vitro and in vivo electrophysiology, optogenetics, and behavior in mouse models of movement disorders with a goal of identifying the patterns of aberrant neural activity which give rise to involuntary movements. By identifying these patterns and the responsible cellular and synaptic mechanisms, she hopes to identify novel drug or deep brain stimulation targets to restore neural activity patterns and normal movement.
David Raleigh, M.D., Ph.D. David trained in the University of Chicago Medical Scientist Training Program, where he conducted his graduate research with Jerrold Turner, studying the regulatory mechanisms and molecular composition of the tight junction. Following his doctoral dissertation, David studied the role of NF-κB in the DNA damage response as part of an abridged postdoctoral experience with Bakhtiar Yamini while completing medical school. After matriculating to UCSF as a resident physician in the Department of Radiation Oncology, David was accepted into the Holman Research Pathway, a specialized training program that grants trainees in radiation oncology dedicated time for research during residency. As a member of Jeremy Reiter’s lab in Department of Biochemistry and Biophysics at UCSF, David combined his background in molecular and cell biology with the Reiter lab’s expertise in developmental biology, genetics, genomics and biochemistry to gain new insights into the molecular determinants of Hedgehog-associated medulloblastoma. In addition to illuminating how the Hedgehog pathway functions in malignancy, these studies have shed light on the fundamental mechanisms of developmental biology. As a UCSF Physiciant-Scientist Scholar, David will investigate (i) how sterol synthesis and interaction with Smoothened impacts oncogenic and developmental Hedgehog signaling, and (ii) how Hedgehog signaling induces cell proliferation to drive cancer. The goal of his laboratory is to understand the role of developmental signaling pathways in cancer, with a particular emphasis on central nervous system malignancies.
Lawrence Shiow, M.D., Ph.D. Lawrence trained in the UCSF Medical Scientist Training Program and
conducted his graduate work with Jason Cyster, studying mechanisms of T cell trafficking. In collaboration with Jennifer Puck, he discovered a new etiology for severe combined immunodeficiency involving thymic
accumulation of T cells. After completing his Pediatric residency in the Accelerated Research Pathway, he continued with Neonatology fellowship at UCSF and started postdoctoral work in the laboratory of David Rowitch to study developmental gliobiology. He has a Pediatric Scientist Development Program award to investigate the molecular mechanism of oligodendrocyte progenitors maturation arrest by systemic inflammation in newborn white matter injury. As a UCSF Physician-Scientist Scholar, Lawrence will investigate how inflammation impacts glial development and pathways that trigger or dampen inflammation in glia. The goal of his laboratory is to study glial aspects of CNS inflammation and translate findings into neuroprotective therapeutics for neonatal brain injury and neurodegenerative disorders.
David Solomon, M.D., Ph.D. David completed medical and graduate training at Georgetown University School of Medicine, where he performed his thesis research in the lab of Dr. Todd Waldman identifying novel transforming pathways in the brain cancer glioblastoma. He then completed an Anatomic Pathology Residency and Neuropathology Fellowship at UCSF. David's research accomplishments include the discovery of frequent inactivating mutations of the cohesin complex gene STAG2 in glioblastoma, urothelial bladder cancer, and the bone cancer Ewing sarcoma, which define molecular subgroups of these tumors with distinct clinical outcomes. As a UCSF Physician-Scientist Scholar, David is focused on understanding the function of the cohesin complex during tumorigenesis and developing novel targeted therapies for the many cancers harboring cohesin gene mutations. Other ongoing research in the Solomon lab is working to identify the recurrent genetic alterations that drive rare brain tumor variants including choroid plexus tumors, pineal parenchymal tumors, and chordoid gliomas. David's clinical interests focus on diagnostic neuropathology, particularly tumors of the central nervous system, and he has been working with the UCSF Clinical Cancer Genomics Laboratory to advance molecular testing for brain tumors at UCSF.