PRISM Mentors

Katherine Whittaker Ferrara is a Professor of Radiology and the Division Chief for the Molecular Imaging Program at Stanford. She is a member of the National Academy of Engineering and a fellow of the IEEE, American Association for the Advancement of Science, the Biomedical Engineering Society, the World Molecular Imaging Society, the Acoustical Society of America and the American Institute of Medical and Biological Engineering. Dr. Ferrara received her Ph.D. in 1989 from the University of California, Davis. Prior to her PhD, Dr. Ferrara was a project engineer for General Electric Medical Systems, involved in the development of early magnetic resonance imaging and ultrasound systems. Following an appointment as an Associate Professor in the Department of Biomedical Engineering at the University of Virginia, Charlottesville, Dr. Ferrara served as the founding chair of the Department of Biomedical Engineering at UC Davis. Her laboratory is known for work in molecular imaging and drug delivery.

The Poston Lab seeks to understand the biological underpinnings of non-motor symptoms in patients with Lewy Body diseases, such as Parkinson's disease and Lewy Body Dementia. While our primary focus is understanding cognition and dementia, we also study other prominent non-motor symptoms such as psychosis/hallucinations, sleep disruption, orthostatic dysregulation, and others.  A major focus is on the role of co-pathologies, such as Alzheimer's and vascular co-pathologies, and the role of neuro-inflammation, in the development of Lewy Body disease associated non-motor symptoms.  We collect clinical, motor, neuropsychological, biological, genetic, and imaging data on patients and healthy older adults to perform our studies. 

The Sakamoto lab studies normal and aberrant blood cell development. Her research team is interested in the pathogenesis of acute and chronic leukemia, including acute myeloid leukemia and chronic myeloid leukemia. The overall goal of her research is to understand the signaling pathways that lead to leukemia or bone marrow failure. She is also interested in developing new drugs to treat these diseases. Her group experience works with mammalian cells and mouse models of cancer and bone marrow failure syndromes, such as Diamond Blackfan Anemia. There are opportunities to work with physicians, translational researchers, medicinal chemists, and advisors from drug companies with experience in drug development.

Experiments utilize leukemia cell lines, primary mouse and human hematopoietic cells, and mouse models will be used.   Technologies in the lab include standard biochemical techniques (Western blot analysis, real-time PCR, immunoprecipitations), FACs/sorting, colony assays, lentiviral and retroviral transductions, transplantation experiments, xenograft models and bioluminescence, CyTOF, RNA-seq ,ChIP-seq, small molecule and  shRNA/CRISPR library screening. Knowledge in bioinformatics would be helpful for single cell RNA-seq experiments. The intent of these early translational studies is to develop small molecules or peptides into drugs to treat acute leukemia.  Assays to assess toxicity, metabolism, optimization, and mechanism of action of compounds are performed.

Dr. Sakamoto is committed to diversity and has trained many underrepresented high school, undergraduate, medical, graduate students and postdoctoral/MD fellows. She has served on the American Society of Hematology Minority Medical Student Program and was Chair of the Diversity Special Interest Group. She is currently working with SMASH Rising to recruit underrepresented high school graduates and community college students to Stanford to study clinical, translational, and basic hematology. 

The Svensson Laboratory is dedicated to the discovery of new fundamental pathways that regulates cellular and organismal metabolism. The main focus is to identify novel functions for new molecules controlling the regulation of glucose and lipid homeostasis using a combination of genomic, proteomic and physiology approaches.

Professor Gaffney leads a research team focused on femtosecond resolution measurements of chemical dynamics in complex condensed phase systems. This research takes advantage of recent advances in ultrafast x-ray lasers, like the LCLS at SLAC National Accelerator Laboratory, to directly observe chemical reactions on the natural time and length scales of the chemical bond – femtoseconds and Ångströms. This research focuses on the discovery of design principles for controlling the non-equilibrium dynamics of electronic excited states and using these principles to spark new approaches to light-driven catalysis in chemical synthesis.

This research builds on Professor Gaffney’s extensive experience with ultrafast optical laser science and technology. This work began with time- and angle- resolved two photon photoemission studies of electron solvation and localization at interfaces as a graduate student working with Professor Charles Harris at the University of California at Berkeley and extended to multidimensional vibrational spectroscopy studies of hydrogen bonding and ion solvation dynamics in solution during postdoctoral studies with Professor Michael Fayer at Stanford and as an Assistant Professor. The transition to ultrafast x-ray science began in 2004 at SLAC, where he helped establish the first chemical dynamics research program at SLAC.

Our laboratory studies the mechanisms by which highly complex behaviors are mediated at the neuronal level, mainly focusing on the example of dynamic social interactions and the neural circuits that drive them. From dyadic interactions to group dynamics and collective decision making, the lab seeks a mechanistic understanding for the fundamental building blocks of societies, such as cooperation, empathy, fairness and reciprocity. The computations underlying social interactions are highly distributed across many brain areas. Our lab is interested in which specific areas are involved in a particular function, why such an architecture arises and how activity in multiple networks is coordinated. Our goal is to develop a roadmap of the social brain and use it for guiding restorative treatments for conditions in which social behavior is impaired, such as Autism Spectrum Disorders and Schizophrenia.

The Wang Lab takes an interdisciplinary approach to studying fundamental mechanisms controlling gene expression in mammalian cells. Our work shows how epigenetic mechanisms such as DNA methylation, chromatin modifications, and RNA influence chromatin dynamics to affect gene regulation. OUR LAB IS CURRENTLY FOCUSED ON: How various dynamic epigenetic changes in chromatin structure impact gene expression during stem cell pluripotency/self-renewal, cellular differentiation, and reprogramming; How three-dimensional chromosomal structure and dysregulation contribute to development of diseases such as aging and cancer; and How to create novel genome engineering tools to interrogate the noncoding genome and the epigenome.
 
The long-term goal of The Wang Lab is to translate our understanding of these complex mechanisms to studies of human diseases.

How the richly varied cell-types in the human body arise from one embryonic cell is a biological marvel and mystery. We have mapped how human pluripotent stem cells develop into over thirty different human cell-types. This roadmap allowed us to efficiently and rapidly generate human liver, bone, heart and blood vessel progenitors in a Petri dish from pluripotent stem cells. Each of these tissue precursors could regenerate their cognate tissue upon injection into respective mouse models, with relevance to regenerative medicine. In addition to our interests in developmental and stem cell biology, we also harbor an emerging interest in deadly biosafety level 4 viruses, such as Ebola and Nipah viruses.

The Steinmetz group develops experimental approaches to read, edit and write entire genomes across scales. By applying these technologies, members of the lab aim at understanding the genetic basis of complex phenotypes, the mechanisms of transcription, and the molecular systems underpinning disease. One of the most daunting obstacles in biomedicine is the complex nature of most phenotypes (including cancer, diabetes, heart disease and several rare diseases) due to epistatic interactions between multiple genetic variants and environmental influences. Our aim is to transform the way we approach biomedical research, eventually by assigning a function to every nucleotide in the human genome. Along the way, we continually innovate and improve novel genomics technologies, enabling us to achieve our goals faster and more efficiently. For example, we will develop novel tools for precision genome editing, increase the scale and complexity of functional genomics screens, learn how to write genomes with unique traits from scratch, and apply long-read sequencing methods to understand disease mechanisms. Ultimately, we are working towards an era in which we can predict phenotypic traits from genetic and environmental information. Achieving this ambitious goal would have far-reaching implications, from facilitating precision medicine for everyone, and to predicting how natural populations will respond to changing environments.

The gene encoding the p53 transcription factor is the most commonly mutated gene in human cancer, yet we lack a complete understanding of how its loss promotes cancer and how to target this pathway therapeutically. My lab studies p53 in the context of two very deadly and common cancer, pancreatic cancer and lung cancer, to understand how p53 loss promotes tumor initiation and progression. We are investigating not only how p53 mutation changes tumor cells themselves but also how these changes in tumor cells alter the cells of the tumor microenvironment to promote cancer development. We strive to understand p53 function using varied approaches, including mass spectrometry, CRISPR screening, ATAC-sequencing, spatial transcriptomics and in vivo mouse analyses. Using these combined approaches, we are gaining key new insights into the fundamental functions of p53 in vivo, which will ultimately inform us on how to target this critical pathway therapeutically.

The primary goal of this laboratory is to promote the health and well being of children and adolescents with chronic pain and their families. In line with this goal, research projects focus on biological, neurological, cognitive, affective, and social risk and resiliency factors of the pain experience. Projects include brain imaging, longitudinal clinical cohort, and treatment intervention studies.

We study how genetic and environmental factors contribute to biological diversity and adaptation. We are particularly interested in understanding (1) how behavior evolves through changes in brain function and (2) how animal physiology evolves through repurposing existing cellular components.
Our mission is to perform rigorous, ethical, and ecologically relevant science across many areas of organismal biology. We aspire to maintain an environment that fosters creativity, diversity, and inclusion as well as engagement with communities in the areas where we work.
We stand in solidarity with the BlackLivesMatter Movement. Scientists and the institutions we work in are complicit in centuries of racism and we will hold ourselves and our institutions accountable by using lab meetings to reflect on our own privileges and by demanding action from Stanford University. We will continue supporting the careers of our Black colleagues by inviting them to seminars, reading their papers, and promoting their work through collaboration and our social media spaces. We are committed to including classrooms in predominantly Black neighborhoods to our Froggers School Program.

Dr. Cong's group is developing novel technology for genome editing and single-cell genomics, leveraging scalable methods inspired by data science and machine learning and artificial intelligence.

His group has a focus on using these gene-editing tools to study immunological and neurological diseases. His work has led to one of the first FDA-approved clinical trials using CRISPR/Cas9 gene-editing for in vivo gene therapy. More recently, his group invented tools for cleavage-free large gene insertion via mining microbial recombination protein (Wang et al. 2022), and developed single-cell perturbating - tracking approach for studying cancer immunology and neuro-immunology (Hughes et al. 2022). We have also strong interest in using deep learning for predicting and designing gene-editing system and protein function (Hughes et al. 2022 and Yuan et al. 2023). Dr. Cong is a recipient of the NIH/NHGRI Genomic Innovator Award, a Baxter Foundation Faculty Scholar, and has been selected by Clarivate Web of Science as a Highly Cited Researcher.

We work on technology development for genome engineering, discovery-focused synthetic biology, and epigenetic gene therapy. We aim to develop new technologies for studying the mammalian genome and treating complex diseases.

For technology development, we are interested in novel technologies that reprogram the mammalian genome and epigenome. We developed the first nuclease-dead dCas9 from the natural CRISPR-Cas9 nuclease. We developed a series of CRISPR tools that greatly enriched the CRISPR toolbox and expanded genome engineering beyond editing. These tools include CRISPR interference (CRISPRi) and CRISPR activation (CRISPRa) for targeted gene activation and repression, LiveFISH for live imaging of DNA and RNA, CRISPR-GO for manipulating the 3D genome organization, and miniature Cas (CasMINI) and hyper-efficient Cas12a (hyperCas12a) for in vivo applications. We harness natural molecules for molecular engineering and evolve novel functions. These tools are broadly used by the community for research and and translational applications.

For discovery-focused synthetic biology, we apply synthetic biology to design and engineer molecules and molecular circuits in mammalian cells. We use synthetic systems to study how cells can be rationally designed as an 'engineering' entity and be harnesses for disease treatment. For example, we engineer T cells to detect new antigens to kill cancer cells or stem cells to integrate environment cues to determine cell fate. By engineering at the scale from molecular to cellular to organismal level, we hope to make synthetic biology a better discovery tool.

For epigenetic gene therapy, we combine epigenome engineering, synthetic biology, and disease models to develop novel therapy to treat cancer, neurodegeneration, and complex genetic diseases. We aim to reveal the importance of noncoding elements including enhancers in the regulation of genome and disease. We harness safe and powerful tools to precisely rewrite the epigenome marks to reverse or cure diseases. We developed PAC-MAN as a treatment to influenza and broad variants of SARS-CoV-2. We aim to greatly expand genome and epigenome engineering towards neurodegenerative diseases and complex diseases.

The human brain contains about 100 billion neurons, each making thousands of synaptic connections. While individual neurons can themselves perform sophisticated information processing, it is the assembly of neurons into circuits via specific patterns of synaptic connections that endows our brain with the computational capacity to sense, act, think, and remember.

How are neurons organized into specialized circuits to perform specific functions? How are these circuits assembled during development? We are investigating these questions in the brains of the fruit fly (~100 thousand neurons) and mouse (~100 million neurons). We have developed molecular-genetic and viral tools, and are combining them with transcriptomic, proteomic, physiological, and behavioral approaches to study these problems.

How do cells in our nervous system develop highly specialized functions after birth, and how do they degenerate as we age? An emerging molecular mechanism is 3D genome architecture—the folding of 6 billion base pairs of DNA (~2 meters) into a tiny cell nucleus (~10 microns). This folding can strategically position genes and their regulatory elements in 3D to orchestrate dynamic gene expression, and has been implicated in many developmental and degenerative diseases (e.g., autism, schizophrenia, Alzheimer’s). However, traditional technologies and algorithms struggle to capture the full complexity of genome architecture of a single cell, and the enormous heterogeneity between cells. In addition, most studies interrogate genome architecture in vitro, taking cells out of their physiological context. The Tan Laboratory of 3D Genomics at Stanford Neurobiology studies the single-cell 3D genome architectural basis of neurodevelopment and aging by developing the next generation of in vivo multi-omic assays and algorithms, and applying them to the human and mouse cerebellum and beyond (e.g., cancer, immunology).

Mature organs respond to the body's changing needs by moving between different 'states' of cellular flux.
The same organ exhibits different kinds of cell flux over time. This is because flux is dynamically tuned to optimize organ function. At homeostasis, cell addition balances loss, giving rise to equilibrium. Upon environmental change, transient disequilibrium promotes physiological growth or shrinkage. When disequilibrium becomes chronic, it leads to pathogenic resizing and disease. We conceptualize these differences as 'organ states' that form a phase space.

What does organ-scale cellular flux look like, and how do these dynamics arise?
We know many molecular signals that impact cellular flux. Yet, we have scarcely begun to discover how these signals alter the 'lifecycle' of individual cells or understand how cells' life cycles integrate to create diverse organ states. For most organs, even basic spatiotemporal features of these cell behaviors remain mysterious.

Our goal is to explain—and ultimately even predict—how large populations of individual cells act to create diverse organ states in response to external change. We believe that the cell dynamics of adult organs can be understood in the granular way that we currently understand embryonic gastrulation. Toward this vision, we build new experimental approaches and conceptual models to decipher how cell life cycles and molecular signaling together create the organ phase space.

The fly gut is our testing ground for probing cell dynamics at the organ-scale…
The adult Drosophila midgut, or fly gut, is a stem-cell based digestive organ. Its relative simplicity (~10,000 cells), extreme genetic tractability, and ease of handling make it ideal for exploring how single-cell behaviors scale to produce whole-organ phenotypes. Because the organ phase space and the cellular life cycle are general features of adult organs, the lessons we learn from the fly gut will provide a general template for organs in other animals, including humans.

…and is a powerful model to study how dynamic cell flux maintains healthy organ form.
The fly gut is also an archetypical example of an epithelial tube, which is both the most primitive organ form and the form of most organs in our own bodies. As our ability to grow human organs in a dish becomes closer to reality, understanding how general principles of epithelial organization operate with the particular dynamics of adult organs becomes crucial for designing better, safer organ therapies. We leverage these well-understood principles of epithelial organization in order to study how the dynamics of cellular flux in the fly gut both reinforce and respond to organ shape.

We are a computational neuropsychiatry lab dedicated to developing computational methods to better understand brain’s overall dynamical organization in healthy and patient populations. We employ algorithms from a wide range of fields, including Applied Mathematics, Econometrics, Machine Learning, Biophysics, and Network Science.

We have immediate multiple openings for postdoc and research engineer/scientist positions. Please contact Dr. Manish Saggar (saggar@staford.edu), Assistant Professor (Research) of Psychiatry and Behavioral Sciences (Interdisciplinary Brain Science Research), for any questions and for applications. 

See here for more details - https://braindynamicslab.github.io/misc/join/

 

The overarching goal of Brain Dyanamics Lab is to develop computational methods that could allow for anchoring psychiatric diagnosis into biological features (e.g., neural circuits, spatiotemporal neurodynamics). The lab is funded through an NIH Director’s New Innovator Award (DP2), an NIMH R01, and a faculty scholar award from Stanford’s Maternal and Child Health Research Institute. Our lab excels in developing data-driven computational methods to generate clinically and behaviorally relevant insights from high-dimensional biological data (e.g., neuroimaging) without necessarily averaging the data at the outset. The lab also actively pursue developing novel technologies for experimental design and data collection for enhancing human cognition (e.g., creativity and collaboration). Lastly, the lab also uses large-scale biophysical network modeling approaches to study effects of neuromodulation via TMS and pharmacology (e.g., psychedelics).

We study the genetic and molecular mechanisms that regulate proliferation and differentiation in adult stem cell lineages, using the Drosophila male germ line as a model.  Our current work is focused on the switch from mitosis to meiosis and how the new gene expression program for cell type specific terminal differentiation is turned on.  One emerging surprise is the potential role of alternative processing of nascent mRNAs in setting up the dramatic change in cell state

We study the genetic and molecular mechanisms that regulate proliferation and differentiation in adult stem cell lineages, using the Drosophila male germ line as a model.  Our current work is focused on the switch from mitosis to meiosis and how the new gene expression program for cell type specific terminal differentiation is turned on.  One emerging surprise is the potential role of alternative processing of nascent mRNAs in setting up the dramatic change in cell state

Roncarolo laboratory is exploring the basic biology and translational applications of human type 1 regulatory cells (Tr1). We are using engineered Tr1, ex vivo Tr1, and alloantigen-specific Tr1 to uncover the molecular frameworks that govern Tr1 identity, differentiation and function. We are also translating Tr1 into the clinic. First, Tr1 can be used as a supportive cell therapy to enhance stem cell engraftment and immune reconstitution after hematopoietic stem cell transplantation (HSCT). Alloantigen-specific Tr1, designed to prevent graft-vs-host disease (GvHD) after allogeneic HSCT, are already being tested in a phase I/II clinical trial (NCT03198234). Second, we are investigating the mechanisms of action and clinical potential of the engineered Tr1 called CD4(IL-10) or LV-10, generated by lentiviral transduction of CD4 T cells with IL10 gene. Besides their immunosuppressive and anti-GvHD properties, LV-10 lyse primary acute myeloid leukemia (AML) cells and delay myeloid leukemia progression in vivo. We are exploring LV-10 as a novel cell immunotherapy for AML. Finally, we are interested in curing inborn errors of immunity by stem cell transplantation or autologous stem cell gene correction. We are testing a gene editing strategy to correct pathogenic mutations in IL10 and IL10 receptor genes, which cause severe and debilitating VEO-IBD (very early onset inflammatory bowel disease) in infants and young children.

Roncarolo laboratory is exploring the basic biology and translational applications of human type 1 regulatory cells (Tr1). We are using engineered Tr1, ex vivo Tr1, and alloantigen-specific Tr1 to uncover the molecular frameworks that govern Tr1 identity, differentiation and function. We are also translating Tr1 into the clinic. First, Tr1 can be used as a supportive cell therapy to enhance stem cell engraftment and immune reconstitution after hematopoietic stem cell transplantation (HSCT). Alloantigen-specific Tr1, designed to prevent graft-vs-host disease (GvHD) after allogeneic HSCT, are already being tested in a phase I/II clinical trial (NCT03198234). Second, we are investigating the mechanisms of action and clinical potential of the engineered Tr1 called CD4(IL-10) or LV-10, generated by lentiviral transduction of CD4 T cells with IL10 gene. Besides their immunosuppressive and anti-GvHD properties, LV-10 lyse primary acute myeloid leukemia (AML) cells and delay myeloid leukemia progression in vivo. We are exploring LV-10 as a novel cell immunotherapy for AML. Finally, we are interested in curing inborn errors of immunity by stem cell transplantation or autologous stem cell gene correction. We are testing a gene editing strategy to correct pathogenic mutations in IL10 and IL10 receptor genes, which cause severe and debilitating VEO-IBD (very early onset inflammatory bowel disease) in infants and young children.