PRISM Mentors

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.

Our research lab focuses on studying the molecular mechanisms of ion channels and transporters. We use a combination of biophysical methods to probe membrane protein structure and dynamics, together with functional assays and electrophysiological analysis. Ongoing projects in our lab include:
• Examining the molecular mechanisms of chloride/proton transporters
• Developing new small-molecule probes to studying mammalian chloride channels
• Exploring the biophysics and physiology of the mammalian chloride channels
• Using electrophysiology techniques to study the molecular effects of ultrasound neuromodulation on ion channels in brain tissue

Department URL:

https://med.stanford.edu/mcp.html

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.

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.

We discover and elucidate new Ca2+-regulated signaling pathways in humans by studying calcineurin, the conserved Ca2+/calmodulin-regulated protein phosphatase. The calcineurin phosphatase dephosphorylates proteins only when Ca2+ signaling is triggered, for example by a hormone, growth factor, neurotransmitter etc. Previous work from the Cyert lab showed how calcineurin allows yeast cells to survive environmental stress (Goldman et al, 2014, Molecular Cell). Currently, we are studying human calcineurin which is ubiquitously expressed and plays critical roles throughout the body, but especially in the nervous, cardiac and immune systems. Calcineurin is best known for activating the adaptive immune response by dephosphorylating the NFAT transcription factors, and is the target of widely prescribed immunosuppressant drugs, FK506 (tacrolimus) and Cyclosporin A. However, these drugs cause many adverse effects due to inhibition of calcineurin in non-immune tissues, where the majority of calcineurin substrates and functions remain to be discovered. We are using a variety of experimental and computational strategies to systematically map human calcineurin signaling pathways in healthy and diseased cells. These rely on identifying Short Linear peptide Motif (SLiMs), i.e. highly variable sequences that reside in regions of intrinsic disorder and mediate specific interactions of substrates and regulators with calcineurin. These approaches have revealed surprising roles for calcineurin  that we are currently studying: in Notch signaling, trafficking though nuclear pores, at centrosomes/cilia, and in regulating phosphoinositide signaling at membranes. A new project is studying calcineurin's role in pancreatitis, where we are identifying calcineurin substrates that mediate the major pathophysiological events that occur during pancreatitis.  We are also interested in understanding how reversible protein lipidation (palmitoylation) is regulated and how palmitoylation impacts calcineurin signaling at membranes by modifying calcineurin itself and some of its regulators.

To learn more about our studies, see our recent papers: Wigington, Roy et al, 2020, Molecular Cell (https://pubmed.ncbi.nlm.nih.gov/32645368/) and Ulengin-Talkish et al, Nature Communications (https://www.nature.com/articles/s41467-021-26326-4).

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).

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).

If mood symptoms are identified early in life, the opportunity exists to prevent them from progressing to more disabling chronic conditions. Dr. Singh has developed a scientifically-informed comprehensive framework to accurately diagnose and treat childhood-onset depression and other mood disorders before or soon after they present. The Pediatric Emotion And Resilience Lab uses a multimodal neurobiological approach combining neuroimaging, affective neuroscience, and rigorous clinical assessment to understand the mechanisms of risk and resilience in children. We are looking for postdoctoral candidates from the fields of psychiatry, psychology, pediatrics, neurology, genetics, neuroscience, developmental biology, computer science and related fields who seek to improve or expand their ability to conduct interdisciplinary and translational research in pediatric mood disorders.

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

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.

The laboratory of Dr. Marlene Rabinovitch, Professor of Pediatrics (Cardiology) is seeking a highly-motivated and accomplished postdoctoral scholar to join their team of investigators  in conjunction with the Basic Science and Engineering (BASE) Initiative  of the Children’s Heart Center at Stanford University.

A successful applicant will be immersed in cutting-edge molecular, sequencing, imaging and high throughput ‘omics’  technologies applied to human vascular and immune cells  and in their application  to mouse and rat models of  human vascular disease with a focus on pulmonary arterial hypertension.  Our research interests relate to the impact of metabolic reprogramming on gene regulation and RNA translation, the impact of changes in shear stress and DNA damage on the epigenome, bioengineering blood vessels, immune and vascular cell interactions .  We incorporate transgenic models of disease, iPSC generated vascular and immune cells, gene editing, high-throughput drug testing, single cell RNA Sequencing and high dimensional single cell mapping of tissues.  Please consult our website for more details.

All our projects offer opportunities for co-mentoring in Basic, Engineering and Cardiovascular Science.

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.

My work focuses on neuroimmunology and how the central and peripheral immune system responds to brain injury, and in particular, stroke. We study how microglia and astrocytes respond with an emphasis on both the basic biology and clinically-relevant outcomes. We are also interested in how stroke can provoke long-lasting adaptive immune responses that lead to post-stroke dementia, a serious and currently untreatable consequence of stroke. The basic science lab performs primarily studies in mice and on human samples, while the Stanford Stroke Recovery Program (https://med.stanford.edu/neurology/divisions/stroke/recovery.html) enrolls stroke survivors and collects clinical data and human samples to ask whether findings in mice are applicable to humans. My lab values diversity of all types and there are projects available for postdoctoral scholars either in mouse or human studies.

The Skylar-Scott Lab specializes in cardiovascular tissue biomanufacturing, seeking to push the complexity and scale at which tissue can be designed and manufactured on demand. By integrating high-throughput culture of designer organoids with new machines and methods for advanced 3D bioprinting, our laboratory seeks to enhance the maturation and function of vascularized cardiac tissues in vitro and in vivo.

Our lab is embedded at the intersection of synthetic biology, tissue engineering, and 3D printing. We are always seeking new students and postdocs with a demonstrated passion for rethinking how we make things, with relevant expertise in bioengineering, mechanical engineering, or materials science.

Small molecules from the human microbiota. Many of the most widely used human medicines come from soil and marine bacteria, including treatments for cancer, infectious disease, diabetes, and organ transplant. We have recently found that bacteria from a surprisingly underexplored niche -- the human body -- are prolific producers of drug-like small molecules. We are identifying small molecules from gut- and skin-associated bacteria, studying their biosynthetic genes, and characterizing the roles they play in human biology and disease. 
 
Using synthetic ecology to control microbiome metabolism. One of the most concrete contributions the microbiome makes to human biology is to synthesize dozens of metabolites, many of which accumulate in human tissues at concentrations similar to what is achieved by a drug. We are engineering gut and skin bacterial species to produce new molecules, and constructing synthetic communities whose molecular output is completely specified.

I am a physician scientist with interests in cardiomyopathies, rare and undiagnosed diseases, therapeutics and genomics. I have research training in myocardial and skeletal muscle biology and genetics, genomics, and multi-scale networks. In addition to my research training, I am a physician with interest and experience treating patients with hypertrophic cardiomyopathy, neuromuscular disease associated cardiomyopathies, and inherited dilated cardiomyopathies. I have clinical training in medicine, cardiology, cardiovascular genetics, and advanced heart failure and transplant cardiology. I have extensive translational science efforts, as site PI for ongoing clinical trials for hypertrophic cardiomyopathy and dilated cardiomyopathy and for cardiomyopathy consortia including NONCOMPACT, PPCM and the Precision Medicine Study/DCM Consortium. I am Co-PI of Stanford’s NIH-funded Center for Undiagnosed Diseases, a clinical site of the Undiagnosed Diseases Network. I am also Co-PI of the NIH-funded Bioinformatics Center of the Molecular Transducers of Physical Activity Consortium. I pursue projects and collaborations at the intersection of striated muscle genetics, genomics, therapeutics and clinical investigation.

Department URL:
https://med.stanford.edu/cvmedicine.html

With a creative, collaborative, biophysical mindset, we aim to understand the ability of parasites to interface with their host-cell to a point at which we can exploit the mechanisms not only for finding cures against the disease the parasites cause but also to make parasite mechanisms a tool that we can use to engineer the host’s cells. By developing approaches that allow a quantitative understanding and manipulation of molecular transport our research transforms parasites from agents of disease to tools for health.

Specifically, we are studying how the malaria parasite takes control over red blood cells. By learning the biophysical principles of transport in between the host and the parasite we can design ways to kill the parasite or exploit it to reengineer red blood cells. The transport we study is broadly encompassing everything from ions to lipids and proteins. We use variations of quantitative microscopy and electrophysiology to gain insight into the unique strategies the parasite evolved to survive.

Our research is concerned with the computational modeling and the experimental investigation of fluids in complex environments, including chemical reactions, phase transition, and heterogeneous flow environment. We addressing fundamental scientific questions, problems pertaining to energy-conversion and propulsion, as well as environmental issues related to wildfire predictions, carbon-capture and sequestration, and water desalination. We are developing advanced numerical algorithms, detailed physical models, and physics-informed and data-driven methods. Experimentally, our research employs X-ray absorption and scattering techniques  that involve X-ray Computed Tomography at laboratory and synchrotron sources, X-ray spectroscopy, and ultrafast X-ray techniques at the Linac Coherent Light Source to observe processes at sub-picosecond timescales.

Department URL:
https://me.stanford.edu

The overarching research goal of the Diehn lab is to develop and translate novel diagnostic assays and therapies to improve personalized treatment of cancer patients. We have a major focus on the development and application of liquid biopsy technologies for human cancers, with a particular emphasis on lung cancers and circulating tumor DNA (ctDNA). We also investigate mechanisms of treatment resistance to radiotherapy, immunotherapy, and targeted agents. Most of our research projects start by identifying an unmet need in the clinical management of cancer patients that we then try to solve via development or application of novel technologies. We use genomics, bioinformatics, stem cell biology, genome editing, mouse genetics, and preclinical cancer models in our work. Discoveries from our group are currently being tested in multiple clinical trials at Stanford and elsewhere in order to translate them into the clinic.

The overarching research goal of the Diehn lab is to develop and translate novel diagnostic assays and therapies to improve personalized treatment of cancer patients. We have a major focus on the development and application of liquid biopsy technologies for human cancers, with a particular emphasis on lung cancers and circulating tumor DNA (ctDNA). We also investigate mechanisms of treatment resistance to radiotherapy, immunotherapy, and targeted agents. Most of our research projects start by identifying an unmet need in the clinical management of cancer patients that we then try to solve via development or application of novel technologies. We use genomics, bioinformatics, stem cell biology, genome editing, mouse genetics, and preclinical cancer models in our work. Discoveries from our group are currently being tested in multiple clinical trials at Stanford and elsewhere in order to translate them into the clinic.

I am a clinical pathologist and assistant professor in the Departments of Medicine, Pathology, and Genetics (by courtesy) at Stanford. I completed my MD-PhD training at Yale University and my residency training and a post-doctoral fellowship in the Department of Genetics at Stanford University. My experiences as a clinical pathologist and genome scientist have made me passionate about applying cutting-edge technologies to primary patient specimens in order to characterize disease pathologies at the molecular level. The core focus of my lab is to study the mechanisms by which genetic variants influence the risk of disease through effects on intermediate molecular phenotypes.

Maya Mathur is an Assistant Professor at the Stanford University Quantitative Sciences Unit and the Associate Director of the Stanford Center for Open and Reproducible Science. She is a statistician whose methodological research focuses on advancing methods for meta-analysis, replication studies, and sensitivity analysis. She has received early-career and young investigator awards from the Society for Epidemiologic Research, the Society for Research Synthesis Methods, and American Statistical Association.

The mission of the Water & Energy Efficiency for the Environment Lab (WE3Lab) is to reduce the cost and carbon intensity of water desalination and reuse. Ongoing research efforts include:

1) developing automated, precise, robust, intensified, modular, and electrified (A-PRIME) water desalination technologies to support a circular water economy;

2) optimizing the coordinated operation of decarbonized water and energy systems; and

3) supporting the design and enforcement of water-energy-food policies (e.g., Effluent Limitation Guidelines, the Clean Power Plan, CA Sustainable Groundwater Management Act, etc.).

The mission of the Water & Energy Efficiency for the Environment Lab (WE3Lab) is to reduce the cost and carbon intensity of water desalination and reuse. Ongoing research efforts include:

1) developing automated, precise, robust, intensified, modular, and electrified (A-PRIME) water desalination technologies to support a circular water economy;

2) optimizing the coordinated operation of decarbonized water and energy systems; and

3) supporting the design and enforcement of water-energy-food policies (e.g., Effluent Limitation Guidelines, the Clean Power Plan, CA Sustainable Groundwater Management Act, etc.).

The mission of the Water & Energy Efficiency for the Environment Lab (WE3Lab) is to reduce the cost and carbon intensity of water desalination and reuse. Ongoing research efforts include:

1) developing automated, precise, robust, intensified, modular, and electrified (A-PRIME) water desalination technologies to support a circular water economy;

2) optimizing the coordinated operation of decarbonized water and energy systems; and

3) supporting the design and enforcement of water-energy-food policies (e.g., Effluent Limitation Guidelines, the Clean Power Plan, CA Sustainable Groundwater Management Act, etc.).

Meghan Halley, PhD, MPH, (she/hers) is an Assistant Professor at the Stanford Center for Biomedical Ethics. A medical anthropoloigst by training, her group employees methods from a wide range of disciplines to undersamd ethical and social challenges in research and clinical care for patients with rare and undiagnosed genetic conditions.

I design, build, and study social computing systems: the computational systems that mediate our social interactions with one another. My research sits in an area known as human-computer interaction (HCI).

How do we learn to communicate using language? I study children's language learning and how it interacts with their developing understanding of the social world. I am interested in bringing larger datasets to bear on these questions and use a wide variety of methods including eye-tracking, tablet experiments, and computational models. Recent work in my lab has focused on data-oriented approaches to development, including the creation of large datasets like Wordbank and MetaLab. I also have a strong interest in replication, reproducibility, and open science; some of our research addresses these topics.

http://web.stanford.edu/~mcfrank

Our research is focused on structural characterization of materials used for energy conversion and storage and for desalination. We use X-ray techniques at SSRL to establish structure-function relationships in complex materials.

Our lab is broadly interested in how intestinal microbes shape our immune system to promote both health and disease. Recently we discovered that a type of intestinal epithelial cell, called tuft cells, act as sentinels stationed along the lining of the gut. Tuft cells respond to microbes, including parasites, to initiate type 2 immunity, remodel the epithelium, and alter gut physiology. Surprisingly, these changes to the intestine rely on the same chemosensory pathway found in oral taste cells. Currently, we aim to 1) elucidate the role of specific tuft cell receptors in microbial detection. 2) To understand how protozoa and bacteria within the microbiota impact host immunity. 3) Discover how tuft cells modulate surrounding cells and tissue.

Specificity and efficacy in intracellular signal transduction can be conferred by the anchoring and co-localization of key enzymes and their upstream activators and substrate effectors by scaffold proteins. The Kapiloff lab investigates “signalosomes” formed by scaffold proteins, asking fundamental questions such as: 1) how are signalosomes constituted; 2) how are upstream signals integrated by signalosomes to regulate in a concerted manner downstream effectors; 3) what is the physiologic relevance of these signalosomes; and 4) can signalosomes be targeted in a clinically relevant manner so as to constitute new therapeutic strategies. In particular, the Kapiloff lab studies signaling within the myocardium and retina. Using a comprehensive approach that includes biochemistry, cell biology, and in vivo physiology, ongoing projects address the regulation of pathological cardiac remodeling and the effects of disease on retinal neurons.