Current Fellows

UCSF Sandler Fellows:

Mustafa Aydogan, D. Phil. Mustafa is fascinated by how biological time is regulated across different scales, with a particular interest in the regulation of organelle biogenesis. He carried out his doctoral work at the University of Oxford to study how centriole biogenesis is regulated in space and time. In particular, he discovered that an autonomous clock controls the timing of centriole formation – independently of, but in entrainment with, the principal Cdk/Cyclin cell-cycle oscillator. This finding challenges the current model of how cell cycle is regulated and opens a potential new avenue of research to explore whether other such autonomous clocks exist in the cell. The Aydogan Lab currently focuses on timing mechanisms that may be at play in the biogenesis of other organelles. They use state-of-the-art techniques in live super-resolution microscopy, combined with genetics, biochemistry, biophysics and mathematical modelling, to address biological phenomena.

 

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.

 

 Margaux Pinney, Ph.D. Margaux received her Ph.D. from the Department of Biochemistry at Stanford University. As a graduate student in Dr. Daniel Herschlag’s lab, she studied the molecular mechanisms of enzyme temperature adaptation. This work ultimately tested and refined most existing models of enzyme temperature adaptation and identified new molecular mechanisms for enzyme stability and activity in >1000 enzyme families. Margaux then joined the laboratories of Dr. Polly Fordyce and Dr. Gavin Sherlock at Stanford to adapt and develop methods for mapping between protein function and organism fitness in high throughput. The Pinney Lab studies the molecular mechanisms that allow organisms and their proteins to adapt to new and changing environments, with a focus on temperature adaptation. They use high-throughput biochemistry and organism fitness methods to integrate information across biological scales. The central goals of this work are to: (1) reveal enigmatic aspects of protein function to inform their design principles and (2) provide a fundamental understanding of organism adaptation, which is critical for understanding processes such as adaptation to climate change.

 

reeves-headshotMelissa Reeves, 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.

 

Caroline Vissers, Ph.D. Caroline received her PhD from the Biochemistry, Cellular and Molecular Biology program at Johns Hopkins School of Medicine. Her work in the lab of Hongjun Song was the first to show the regulatory effect of chemical modifications on mRNA, termed “epitranscriptomics,” on mammalian cortical neurogenesis. One methylation in particular, m6A, regulates neural stem cell proliferation and differentiation and allows for pre-patterning of neural stem cell fate prior to differentiation. Additionally, Caroline collaborated with Gregg Semenza to study how m6A regulates breast cancer cell response to hypoxia. She showed that stress-induced dynamics of m6A regulate cancer cell gene expression at both RNA and protein levels, with consequences in cell proliferation and metabolism. As a UCSF Sandler Fellow, Caroline will lead a research program studying how the epitranscriptome is regulated, particularly in response to endogenous (developmental signaling pathways) and exogenous (stress) stimuli. This work will be applied to studies of neural development and disease with the ultimate goal of developing new therapies for developmental and neurodegenerative disorders.

 

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.

 

Andrew Yang, Ph.D. Andrew’s goal is to understand and engineer healthy brain homeostasis. As a graduate student in Tony Wyss-Coray's lab at Stanford University, he developed new proteome tagging and single-cell approaches to discover unexpected communication across the blood-brain barrier (BBB), mechanisms of its impairment with age, and its links to Alzheimer's disease. As a UCSF Sandler Fellow, Andrew and his lab develop new molecular approaches to decode the meaning, mechanisms, and therapeutic relevance of protein and immune crosstalk between the brain and body. The lab uses a combination of proteomics, chemical biology, single-cell sequencing, imaging, and functional approaches. By deciphering the general principles by which the periphery communicates with the brain, this work could enable new approaches to engineer greater resilience against brain aging and neurodegeneration.

 

Affiliated Fellows:

 

QBI Fellows: The QBI (Quantitative Biosciences Institute) Fellowship attracts early-career scientists who are on the cutting edge of new technologies and discovery.  The fellowship hastens their growth towards independent basic research problems relating to human health and advancement.

 

Willow Coyote-Maestas, Ph.D. Willow did his PhD in Daniel Schmidt’s lab at the University of Minnesota, where he developed massively parallel sequencing-based methods to study and engineer proteins. Using mutational and insertional scanning methods, Willow found these methods can be useful for identifying regions of a protein involved in functionally meaningful conformational changes, developed mechanistic models for how to assemble protein domains to create useful multi-domain protein tools, and studied the evolution of ion channel regulation. As a QBI Fellow, Willow is inventing high-throughput sequencing-based biophysics and biochemistry methods for understanding how a genetic, chemical, or physical perturbations alters the trafficking or functional state of receptors. The long-term goal of this work is to build mechanistic holistic models of how receptors break in disease and work in normal physiology.

 

Kliment Verba, Ph.D. Klim completed his Ph.D in David Agard’s laboratory at UCSF, training in a variety of biophysical methods with focus in cryo electron microscopy. Recent breakthroughs in the field and novel methods he helped develop in house allowed him to obtain astructure of a chaperone-kinase complex with the kinase being in a previously unseen, partially folded state. Not only this provided the first high resolution structural insight of how Hsp90 chaperone machinery recognizes substrates but also how kinases may use unfolded states for regulation. Key signalling kinases act as parts of larger signalling complexes and it is likely that binding partners other than chaperones utilize the fluidity of the native state to gain fine allosteric regulation of the kinase activity. This is an exciting hypothesis which until recently has been completely out of the realm of structural biology. As a QBI fellow Klim plans to interrogate large, transient and heterogeneous kinase signalling complexes combining methods like cryoEM and mass spectrometry, and where required developing novel methods, to see just how this fluidity may be utilized in signalling.

 

 

California Academy of Sciences Fellow:

Alison Gould, Ph.D. Alison earned her Ph.D. from the University of Michigan in Ecology and Evolutionary Biology where she studied theevolutionary ecology of a bioluminescent symbiosis between a coral reef fish and a luminous bacterium in the Vibrio family. Having established the foundational context with which to study this association at a more mechanistic level, she is currently developing this highly specific, binary association as a new model with which to disentangle the complex mechanisms regulating our gut microbiome. In partnership with the California Academy of Sciences, Alison will study this bioluminescent symbiosis to determine how host-microbe specificity is established and maintained from the broad evolutionary scale down to the molecular level, identifying critical pathways involved in symbiont recognition, integration, and persistence within a host.

 

 

Physician-Scientist Scholar Program: The PSSP was established by the UCSF School of Medicine in partnership with the clinical departments to identify and support young physician/scientists who engage in medical practice and have shown exceptional promise to launch an independent laboratory research program, like UCSF Sandler Fellows. Information on these Fellows can be found here.