PRISM Mentors

Mitochondrial dysfunction is commonly associated with aging and age-related chronic diseases. A major goal of our research is to understand how mitochondrial dysfunction arises during aging and contributes to the pathogenesis of a broad spectrum of age-related diseases, from cancer to neurodegenerative diseases and sarcopenia. An overarching hypothesis is that aging and age-related diseases share  fundamental molecular and cellular mechanisms. Thus, by targeting the molecular drivers of aging, we can develop new understandings and therapies for many age-related diseases. Supporting this hypothesis, our more recent studies demonstrate that reverse electron transport (RET) along mitochondrial electron transport chain is activated during aging, leading to excessive reactive oxygen species (ROS) production and imbalanced NAD+/NADH ratio, and that inhibition of RET is beneficial in disease models of brain tumors and neurodegenerative diseases. We are actively investigating the mechanism of RET activation during aging, the signaling pathways influenced by RET, and the potential of RET as a viable therapeutic target. We use Drosophila and mouse in vivo models, human induced pluropotent stem cell (iPSC) derived cell culture models, and state-of-the art techniques such as CRISPRa/i, proximity proteomics, RNA-seq, cryo-EM, and molecular dynamics simulation in our research.

Research in the Pollack lab centers on translational genomics, with a current focus on diseases of the prostate. The lab employs next-generation sequencing, single-cell genomics, genome editing, and cell/tissue-based modeling to uncover disease mechanisms, biomarkers and therapeutic targets. Current areas of emphasis include: (1) Defining molecular features of prostate cancer that distinguish indolent from aggressive disease; (2) Determining disease mechanisms and new therapeutic targets in benign prostatic hyperplasia (BPH); and (3) Defining disease drivers in rare neoplasms (e.g., ameloblastoma).

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.

Chromatin regulators are highly altered in diseases. Of interest, these proteins are easily targetable by drugs. Furthermore, the plasticity of epigenetic events makes them a powerful target for new therapeutic strategies and reversion of disease phenotype. Histone and DNA modifications influence many processes including transcription, replication, genomic stability and cell division, which are altered in diseases. Therefore, understanding the molecular basis of chromatin modifiers in both normal and pathological cells could help us frame new potential biomarkers and targeted therapies. My long-term interest lies in understanding the impact chromatin modifiers have on disease development and progression so that more optimal therapeutic opportunities can be achieved. My laboratory explores the direct molecular impact of chromatin-modifying enzymes during cell cycle progression, and characterizes the unappreciated and unconventional roles that these chromatin factors have on cytoplasmic function such as protein synthesis. By gaining molecular understanding into the mechanism of action of chromatin modifiers in normal and pathological cells, we will improve our basic knowledge and provide needed insights into new potential targeted therapies in diseases.

Department URL:
https://www.google.com/search?client=safari&rls=en&q=stanford+department+of+pathology&ie=UTF-8&oe=UTF-8

The Yeh Lab studies the apicoplast, a unique plastid organelle in Plasmodium falciparum parasites that cause malaria. We are particularly focused on unbiased chemical and genetic screens to discover new cell biology and therapeutic targets for this important global health disease. Our work highlights the untapped opportunities in exploring divergent biology in non-model organisms, a theme we plan to expand in the lab by studying ocean algae (malaria's cousins!) and their role in the global ecosystem.

Our lab has several major focuses:
1. Using iPSC-derived cardiomyocytes to develop a better understanding of hypertrophic cardiomyopathy and congenital heart disease.
2. The role of alterations in mitochondrial structure and function in normal physiology (such as exercise) and in disease such as dilated and hypertrophic cardiomyopathy.
3. Single cell analysis of mitochondrial function reveals significant heterogeneity.
4. Differences between right and left ventricular responses to stress and in their modes of failure, including gene expression and miR regulation.
5. Use of iPSC-CMs in pharmacogenomics, specifically determining the role of gene variants in doxorubicin cardiotoxicity.

Specific projects underway in our lab include:

1. Alterations of mitochondrial structure and function, including processes of mitofusion, mitofission, autophagy and mitophagy, in normal physiology and disease.

2. Development of high-throughput single cell imaging technologies to measure single cell mitochondrial function, and to measure single mitochondrial function to determine the role of heterogeneity in cell life-death decision-making.

3. Differences between the right and left ventricles in their responses to stresses such as increased afterload and increased preload, including gene expression and gene regulation by micro-RNAs. The use of plasma miRs as biomakers for RV failure.

4. Using patient-derived iPSC-cardiomyocytes to understand the mechanisms of cardiomyopathies common in children and to solve the genotype-phenotype conundrum in hypertrophic cardiomyopathy. The role of altered metabolism and mitochondrial function in hypertrophic cardiomyopathy.

5. Development of micro-engineered platforms for assessment of biomechanics of single iPSC-derived cardiomyocytes.

6. Developing tools to further mature hiPSC-CMs to more accurately recapitulate the mechanobiology of adult human CMS.

We also are interested in clinical heart failure and cardiac transplantation in children, specifically:

1. Understanding alterations in immune system function in patients with after implantation of a left ventricular assist device, Immune system biomarkers that predict adverse outcomes after pediatric VAD implantation.

2. Development of biomarkers for the detection and monitoring of post-transplant lymphoproliferative disorder in pediatric transplant patients.

Our team is committed to finding ways to improve maternal and infant health outcomes and equity by leading research that identifies effective leverage points for change, from upstream 'macro' social and structural factors, to downstream 'micro' clinical factors through a collaborative research approach that integrates epidemiologic approaches with community engagement and systems thinking.

Disparities are prominent in maternal and infant health, so a lot of our work is centered on equity.  Focusing on highest-risk groups will improve health for everyone.

Much of our current research focuses on severe maternal morbidity (SMM). SMM encompasses adverse conditions that put pregnant people at risk of short and long-term consequences related to labor and delivery, including death.

We also study other important perinatal outcomes, including stillbirth, preterm birth, structural congenital malformations and other maternal morbidities.  We are interested in these outcomes individually, as well as in how they are connected to each other -- from a mechanistic standpoint (ie, do they share the same causes), and a lifecourse perspective (eg, how does an adverse newborn outcome affect the mom's postpartum health, and vice versa).

Dr. Carmichael's training is in perinatal and nutritional epidemiology.  She deeply appreciates her multi-disciplinary colleagues who make this work more meaningful by bringing their own varied perspectives and lived experiences, and their expertise in clinical care, qualitative and mixed methods, community engagement, and state-of-the-art epidemiologic approaches and biostatistical methods.

Our research program integrates concepts of chemical biology, protein engineering and structure biology to design new therapeutic leads and generate probes to study biological processes. A key focus of our lab is insulin, an essential hormone in our body to reduce blood glucose levels. We generate synthetic libraries of insulin analogs to select for chemical probes, and investigate natural insulin molecules (e.g. from the venom of fish-hunting cone snails!) to develop novel therapeutic candidates. We are especially interested in using chemical and enzymatic synthesis to create novel chemical entities with enhanced properties, and leverage the strong expertise of our collaborators to apply our skill sets in the fields of cancer biology, immunology and pain research. Our ultimate goal is to translate our discovery into therapeutic interventions in human diseases.

The Davis laboratory is looking for post-doctoral scholars interested in the study of cancer. We use single-cell, high-dimensional approaches in primary patient materials to identify cells associated with poor clinical outcomes. We have a focus on childhood leukemia, neuroblastoma and Ewing sarcoma. Once identified, we can further interrogate mechanisms of resistance in candidate cell populations and develop new approaches for treatment. 

We are looking for motivated and talented computational biologists and cancer biologists with interest in joining our active group. In particular, opportunties for data scientists/computational biologists are available. 

My research focuses on the neurobiological basis of language, reading, and cognition in children.  Functional imaging studies demonstrate that language and reading skills require the integrated activity of a network of distributed brain regions.  Diffusion magnetic resonance imaging (dMRI) documents that variations in the properties of long-range white matter pathways connecting these brain regions within the cerebrum and between the cerebrum and cerebellum are associated with variations in language and reading skills.  These white matter pathways may be disturbed in childhood illnesses, such as brain tumors. We have been collecting dMRI scans on children born preterm and full term at different ages, including infancy.  We also have been collecting clinical scans on children with brain tumors in the cerebellum and posterior fossa. We seek students who want to learn techniques for analyzing dMRI and related imaging methods in children and to link the neurobiological findings to clinical outcomes.  Selected studies include: (1) analyzing white matter pathways in preterm infants at near term age in relation to medical and environmental variables; (2) applying spherical deconvolution to scans of children age 6 to 8 years who are learning to read; (3) evaluating longitudinal change in children with mutism after resection of a posterior fossa brain tumor.

We aim to understand the genetic basis of diabetes and related metabolic conditions and to use this to leverage a better understanding of what causes diabetes and how we can improve treatment options for patients. Our work is predominantly focused on understanding what causes pancreatic islets to release insufficient insulin to control blood glucose levels after a meal in patients with type 2 diabetes, but often extends to efforts to relate this to metabolic dysfunction in other relevant tissues such as fat and liver.

We are an inter-disciplinary team of basic and clinical scientists with shared interests in using molecular genetics as a tool to uncover novel biology. We use a variety of different approaches to address important challenges in the field, which range from studies that work genome wide to those which are focused on specific genes and even precise nucleotide changes to understand their impact on pancreatic islet biology.

We have developed a series of pipelines that use primary human islets and authentic beta-cell models which allow us to generate and then integrate complex genomic, transcriptomic and cellular datasets. We use state-of-the art genome engineering approaches combined with induced pluripotent stem-cells to study the impact of T2D-associated genetic variants on islet cell development and function. We are also funded to investigate the impact of T2D risk variants on pancreatic beta-cell function in vivo.

We are a highly collaborative team and work with multiple national and international consortia involved in efforts to understand the genetic basis of type 2 diabetes (eg DIAGRAM, NIDDK Funded Accelerated Medicines Partnership) and related glycaemic traits (MAGIC). We are also part of several Innovative Medicines Initiatives (IMIs) efforts including STEMBANCC and RHAPSODY and Horizon 2020 initiatives (eg T2DSYSTEMS), which are working to develop tools and frameworks to capitalize on genetic and genomic data.

We are also part of the NIDDK funded Human Islet Research Network (HIRN) where we play a role in two of their initiatives. The Human Pancreas Atlas Program- T2 (HPAP-T2D) and the Integrated Islet Phenotype Program (IIPP). Our role is to support the genetic and genomic characterization of islets which are distributed for research and to support the genomic characterization of the pancreas’ phenotyped within the HPAP-T2D program.

Our work extends to playing a role in the interpretation of genetic variants identified in genes with known roles in monogenic forms of diabetes. We are part of the Clin Gen Expert Review Panel for Monogenic Diabetes where are expertise contributes to interpretation of coding alleles in glucokinase (GCK) and Hepatocyte Nuclear Factor 1 alpha (HNF1A). We are a number of on-going projects which are supporting efforts to better understand how to use exome-sequencing data in a diagnostic setting.

The Kay lab is interested in Gene Transfer, Genome Editing and Non-coding RNA biology.  The current research is studying: 1) rAAV vectors specifically:   developing capsid libraries, chemical modification of  vectors and screening approaches that will provide improved vectors for human application;  molecular mechanism of discordance in vector transduction between species;  molecular mechanisms involved in AAV transduction;  and chromatin formation of gene transfer vector genomes in primary tissues. 2) Approaches to achieve therapeutic levels of  non-nuclease mediated genome editing using rAAV vectors.  3)  Non coding RNAs: association between long-non coding RNAs and miRNA biogenesis in whole tissues;  tRNA derived small RNAs and their role in regulating ribosome biogenesis in cancer; and role of Line1 structural RNAs in controlling gene expression.

We are seeking an individual for a postdoctoral fellowship in perinatal / neonatal health who has training and experience in epidemiology or a related field (e.g. PhD or MD with relevant research training). The primary mentor is Dr. Henry C. Lee, Associate Professor of Pediatrics (Neonatology), and Chief Medical Officer of the California Perinatal Quality Care Collaborative (CPQCC) . The CPQCC and its sister organization, the California Maternal Quality Care Collaborative (CMQCC) have their data centers and leadership based at the division of neonatology at Stanford, and have active research programs in perinatal health. The ability to link maternal, neonatal, and long-term follow-up data allow for opportunities to conduct large population-based epidemiologic studies, health services research, and work in reducing disparities. The emphasis of this fellowship will be on the population of extremely preterm birth, including prediction / modeling of outcomes for periviable infants, and development of tools for counseling families affected by extremely preterm birth. The postdoctoral fellow will collaborate with epidemiologists, biostatisticians, and clinician-scientists, with opportunities for mentorship and collaborative research on related topics.

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.

Current Research and Scholarly Interests
My laboratory's overall goal is to (i) understand the mechanisms of right heart failure in children and adults with congenital heart disease and (ii) to develop biomarkers as a plasma signature of myocardial events to better understand the mechanisms of heart failure, improve monitoring of disease progression, early detection of heart failure and risk-stratification.

We have focused on tetralogy of Fallot population and single ventricle heart disease. As the survival continues to improve, so also has the incidence of heart failure. However, the underlying cellular mechanisms of heart failure are poorly understood as a result of which no targeted therapy is available. Since it is not possible to obtain heart muscle biopsies routinely on patients, we have taken a novel strategy of using Multi-Omics to better understand disease mechanisms and to follow patients over time comparing their Omics signature to themselves thereby personalizing their care. The goal is to create a targeted biomarker panel for clinical utility to be used in conjunction with imaging data to improve overall prediction of risk. Based on our work to date, we are also interested in understanding myocardial mitochondrial and vascular dysfunction as these have the potential to serve as novel therapeutic targets.

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. 

Mission: Our mission is to both use neuroscience as a tool for improving education, and use education as a tool for furthering our understanding of the brain. On the one hand, advances in non-invasive, quantitative brain imaging technologies are opening a new window into the mechanisms that underlie learning. For children with learning disabilities such as dyslexia, we hope to develop personalized intervention programs that are tailored to a child’s unique pattern of brain maturation. On the other hand, interventions provide a powerful tool for understanding how environmental factors shape brain development. Combining neuroimaging with educational interventions we hope to further our understanding of plasticity in the human brain.
The Lab: The Brain Development & Education Lab is located in the Graduate School of Education at Stanford University and represents a collaboration between the Division of Developmental and Behavioral Pediatrics within the School of Medicine, the Graduate School of Education and the Wu Tsai Neuroscience Institute (we recently moved from The University of Washington’s Institute for Learning & Brain Sciences). The focus of the lab is understanding the interplay between brain maturation and cognitive development.  The lab is interdisciplinary, drawing on the fields of neuroscience, psychology, education, pediatrics and engineering to answer basic scientific and applied questions.  Current projects focus on understanding how the brain’s reading circuitry develops in response to education and how targeted behavioral interventions prompt changes in the brain’s of children with dyslexia. A major component of this work is the development of software to measure properties of human brain tissue, localize differences and quantify changes over development.

Together with Tom Shutt, Dan works on the LUX and LZ dark matter experiments to search for dark matter in the form of Weakly Interacting Massive Particles, or WIMPs. The detectors use liquid xenon as a target medium in a time projection chamber, or TPC. The Large Underground Xenon (LUX) experiment is currently operating a 250-kg target in the former Homestake gold mine in the Black Hills of South Dakota. Preparations are underway at SLAC to design and build the 7-ton successor, known as LUX-ZEPLIN (LZ). The group is involved in many aspects of data analysis, detector design, xenon purification, control andreadout systems, and detector performance studies.

Roger has broad interests in particle astrophysics and cosmology. Roger and his group are currently working on studies of gravitational lensing, compact objects (black holes, neutron stars and white dwarfs) and cosmic rays, tackling difficult questions such as the unknown nature of the gamma-ray flares of the Crab Nebula. He is interested in topics which range from pure theory through phenomenological studies to analysis of observational data. Some of his groups research is strongly computational but plenty is not.

Susan is broadly interested in astrophysical magnetism and the physics of the interstellar medium (ISM), from diffuse gas to dense, star-forming regions. Susan’s research tackles open questions like the structure of the Milky Way’s magnetic field, the nature of interstellar turbulence, and the role of magnetism in star formation. These big questions demand multiwavelength observations and new data analysis techniques. Susan is particularly interested in deciphering the magnetic ISM using sensitive measurements of synchrotron and polarized dust emission made by cosmic microwave background experiments like the Atacama Cosmology Telescope (ACT) and the Simons Observatory (SO).

Peter is broadly interested in theoretical physics beyond the Standard Model, including cosmology, astrophysics, general relativity, and even atomic physics. The Standard Model leaves many questions unanswered including the nature of dark matter and the origins of the fundamental fermion masses, the weak scale, and the cosmological constant. These and other clues such as the unification of the forces are a guide to building new theories beyond the Standard Model. Peter's group are interested in inventing novel experiments to uncover this new physics.

The research interests of the molecular imaging instrumentation lab are to create novel instrumentation and software algorithms for in vivo imaging of molecular signatures of disease in humans and small laboratory animals. These new cameras efficiently image radiation emissions in the form of positrons, annihilation photons, gamma rays, and/or light emitted from molecular contrast agents that were introduced into the body and distributed in the subject tissues. These contrast agents are designed to target molecular pathways of disease biology and enable imaging of these biological signatures in tissues residing deep within the body using measurements made from outside the body.

The goals of the instrumentation projects are to advance the sensitivity and spatial, spectral, and/or temporal resolutions, and to create new camera geometries for special biomedical applications. The computational modeling and algorithm goals are to understand the physical system comprising the subject tissues, radiation transport, and imaging system, and to provide the best available image quality and quantitative accuracy.

The work involves designing and building instrumentation, including arrays of position sensitive sensors, readout electronics, and data acquisition electronics, signal processing research, including creation of computer models, and image reconstruction, image processing, and data/image analysis algorithms, and incorporating these innovations into practical imaging devices.

The ultimate goal is to introduce these new imaging tools into studies of molecular mechanisms and treatments of disease within living subjects.

Roger is interested in a variety of topics in high energy astrophysics and cosmology. Much of Roger's group are currently focused on understanding the cosmic gamma-ray sources discovered by the Fermi Space telescope, principally pulsars and blazars. This inherently multi-wavelength question requires them to use telescopes all over the world and in space in order to assemble data on these objects and then to develop and test theoretical models to explain what we see.

Phil's main research interests are in the structure and dynamics of the interior of the sun, how this affect solar activity and through this its effects on terrestrial systems. Phil's group’s primary emphasis is on the structure and dynamics of the solar interior using techniques of helioseismology. His group are interested in both developing instrumentation for solar observatories and in the data analysis of solar magnetic fields from space and from the ground.