PRISM Mentors

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.

Lab website is in creation. Link will be updated when it is ready.

Our lab works on biological mechanisms of patient-specific and disease-specific induced pluripotent stem cells (iPSCs). The main goals are to (i) understand basic cardiovascular disease mechanisms, (ii) accelerate drug discovery and screening, (iii) develop “clinical trial in a dish” concept, and (iv) implement precision cardiovascular medicine for prevention and treatment of patients. Our lab uses a combination of genomics, stem cells, cellular & molecular biology, physiological testing, and molecular imaging technologies to better understand molecular and pathophysiological processes.

My laboratory seeks to identify mechanisms responsible for human congenital heart disease, the most common cause of still-births in the U.S. and one of the major contributors to morbidity and mortality in infants and toddlers. We believe that by understanding the mechanisms regulating growth and differentiation of heart precursor stem/progenitor cells during early embryonic development we can then apply these principles to understand the pathogenesis heart malformation during fetal development and to leverage them for treating adult onset heart diseases such as heart failure and arrhythmia. We currently use both genetically-modified mice as our in vivo model to understand the biology of heart development as well as induced pluripotent stem cells (iPSCs) as a in vitro model to study the process of heart cell formation. Our major areas of interests include cardiovascular developmental biology, disease modeling, tissue engineering, and regenerative biology. Within each of these areas we are particularly focused on understand the major genes that regulate the proper formation of heart chambers and the consequesnces of disrupting the normal expression of these genes and how that may lead to the development of congenital heart diseases. While mouse models are useful for studying the process of heart formation, they are not exactly like the human hearts in various ways. Since human heart fetal tissue are diffulty to obtain, we have chosen to use iPSCs derived from patients with particular congenital heart diseases to study steps involved in human heart malformation. Furthermore, to bring our work closer to treating heart disease patients, we have combined our expertise in stem cell biology with 3D biopring to make engineered functional heart tissue for screening drugs and to serve as replacement tissues for damaged heart muscles.

I am a Professor of Medicine-Oncology and Pathology and the Director of TRAM, ARTS and CTNT Programs.

My laboratory studies how oncogenes such as MYC initiate and maintain cancer.  In partic ular we have shown that shutting down oncogenes even for a brief time can revese cancer or elicit "Oncogene Addiction"  For a recent review of our work please see:

The MYC oncogene - the grand orchestrator of cancer growth and immune evasion Nature Reviews Clinical Oncology, 2022

Members of my laboratory are studying basic mechanisms of Oncogene Addiction, the role of Self-renewal/Stemness, Metabolism, Host Immune System, Protein 
Biogenesis, Microbiome, Extracellular Vesicles.  

We are developing novel therapuetics using small molecules, nanoparticles, proteins/peptides that can be used to target oncogenes and/or restore the immune response against cancer.

We are developing new diagnostic and imaging agents using PET, Mass Spec, Nanoproteomics, MIcrofluidics.

For recent examples of our work please see: Casey et al, Science, 2016; Gouw et al, Cell Metabolism, 2019; Dhanasekaran et al eLife, 2020; Swaminathan et al, Nat Comm 2020.

The Itakura Lab has an immediate opening for a creative and motivated postdoctoral scholar to conduct applied research in the areas of machine learning and pattern/feature detection with a focus on either computer vision/image or genomic/molecular data processing and analysis. The lab focuses on implementing machine learning frameworks and radiogenomic approaches on heterogeneous, multi-scale cancer data (e.g., clinical, imaging, histopathologic, genomic, transcriptomic, epigenomic, proteomic) to accelerate discoveries in cancer diagnostics and therapeutics. Projects include prediction modeling of survival and treatment responses, biomarker (feature) discovery, cancer subtype discovery, and identification of new therapeutic targets. Guided by critical and relevant problems in oncology, these projects have the potential to lead to clinically actionable or translatable findings.

The successful candidate will join the Department of Medicine, Division of Oncology and work. The job description:

• Build and implement algorithms in machine learning applied to either imaging data (computer vision) or genomic/molecular data (computational biology)
• Develop software tools for integrative analysis of heterogeneous, multi-omic cancer data using machine learning
• Publish and present research findings in journals and conferences

Required Qualifications:

• PhD (or MD/PhD) in Computer Science, Engineering, Informatics, Statistics, Applied Physics, or a related field with strong skills in data mining, machine learning, or statistics
• Experience in modeling, integrative analyses, parallel computing, and/or software development desirable
• Biomedical knowledge or research experience is not a requisite
• Demonstrated ability to work independently, problem-solve, author manuscripts, strive for innovation, and be highly self-motivated
• Strong interpersonal and communication skills, and ability to work as part of a multi-disciplinary team

The overall goal of our laboratory is to uncover new regulatory mechanisms in signaling systems, to understand how these mechanisms are damaged in disease states and how to devise new new strategies to repair their function.  Specific areas are highlighted below:

1. The Hedgehog and WNT pathways, two cell-cell communication systems that regulate the formation of most tissues during development. These same pathways play central roles in tissue stem-cell function and organ regeneration in adults. Defects in these systems are associated with degenerative conditions and cancer.

2. Signal transduction at the primary cilium and the mechanism of cilia-associated human diseases. Primary cilia are solitary hair-like projections found on most cells in our bodies that function as critical hubs for signal transduction pathways (such as Hedgehog). Over fifty human genetic diseases, called “ciliopathies,” are caused by defects in cilia. Patients with ciliopathies can show phenotypes in nearly all organ systems, suffering from abnormalities ranging from birth defects to obesity.

3. Regulation of signaling pathways by endogenous lipids. The landscape of endogenous small-molecules and their biological functions remains a terra incognita, one that provides many opportunities to discover new regulatory layers in signaling pathways and other membrane dependent processes.

4. Biomolecular condensates in cancer and cancer therapeutics. The formation of reversible, membrane-less compartments in cells by the segregation of proteins into liquid phases, hydrogels or amyloid-like assemblies is an emerging principle of cellular organization. Emerging evidence shows that some cytotoxic drugs used in oncology can accumulate in and disrupt the biophysical properties of these condensates. A future challenge is to develop strategies to target such membraneless compartments (such as the nucleolus) for effective and safe cancer therapies.

5. Cellular adaptation to extreme tissue environments. Many cells in our bodies can be considered “extremophiles,” charged with maintaining homeostasis in the face of an environment containing markedly non-physiological concentrations of ions, small molecules and toxins. For instance, cells in the kidney medulla face tissue concentrations of ions, urea and other small molecules that are several-fold higher than blood.

Our lab uses cellular, biochemical, and genetic approaches to understand the mechanism by which developmental signaling pathways, such as the WNT and Hedgehog pathways, function and how they are damaged in disease states. We use a broad range of approaches in our work: genome-wide CRISPR screens, proteomics, imaging, and both protein and lipid biochemistry.

Vast amounts of molecular data characterizing the genome, epi-genome and transcriptome are becoming available for a wide range of complex disease such as cancer and neurodegenerative diseases. In addition, new computational tools for quantitatively analyzing medical and pathological images are creating new types of phenotypic data.  Now we have the opportunity to integrate the data at molecular, cellular and tissue scale to create a more comprehensive view of key biological processes underlying complex diseases. Moreover, this integration can have profound contributions toward predicting diagnosis and treatment. The Gevaert lab focuses on achieving progress in multi-scale modeling by tackling challenges in biomedical multi-scale data fusion. Applications are in the area of complex diseases with most projects in the lab focused on oncology, and possible new directions studying neuro-degenerative & cardiovascular diseases.

Our group combines computational and experimental techniques to study the cellular organization of complex tissues, with a focus on determining the phenotypic diversity and clinical significance of tumor cell subsets. We have a particular interest in developing innovative data science tools that illuminate the cellular hierarchies and stromal elements that underlie tumor initiation, progression, and response to therapy. As part of this focus, we develop new algorithms to resolve cellular states and multicellular communities, tumor developmental hierarchies, and single-cell spatial relationships from genomic profiles of clinical biospecimens. Key results are further explored experimentally, both in our lab and through collaboration, with the goal of translating promising findings into the clinic.

As a member of the Department of Biomedical Data Science and the Institute for Stem Cell Biology and Regenerative Medicine, and as an affiliate of graduate programs in Biomedical Informatics, Cancer Biology, and Immunology, we are also interested in the development of impactful biomedical data science tools in areas beyond our immediate research focus, including developmental biology, regenerative medicine, and systems immunology.

Statistical algorithms for genomics, RNA biology, splicing, cancer genomics, spatial transcriptomics

Several studies have now shown the importance of Wnt signaling for heart tissue repair in the left ventricle, but fewer studies have been done to understand Wnt’s role in right ventricle hypertrophy. The remodeling of the right ventricle during pulmonary hypertension leads to changes and impairment in the vasculature, cardiomyocyte dysfunction and fibrosis.  Our lab has shown the importance of Wnt signaling in pulmonary angiogenesis and we hypothesize that Wnt expression in the cardiac cells is critical to improve their response to the pressure load and with this, prevent heart failure. Using cardiac muscle cells and endothelial cells derived from healthy and idiopathic PH patients; we are screening and comparing the expression of several Wnts between the two groups in order to find Wnt candidates for our study. We aim to find a Wnt-associated gain of function in heart cells after injury during PH

The Stanford Center for Biomedical Ethics (SCBE) is an interdisciplinary hub for faculty who do research, teaching, and service on topics in bioethics and medical humanities. SCBE researchers have pioneered new approaches to studying the ethical issues presented by new technologies in biomedicine, including Artificial Intelligence, CRISPR and Gene Therapy, Stem Cell Research, Synthetic Biology, and the Human Brain Initiative. To benefit patients, SCBE has undertaken novel, ground-breaking research to improve clinical care, including end of life care, communication between patients and physicians, care for disabled patients, and organ transplantation processes. SCBE offers postdoctoral fellowships in Ethical, Legal, and Social Implications (ELSI) Research and Clinical Ethics. We currently have an opening for a postdoctoral fellow in Clinical Ethics. View more information here. 

My lab is focused on understanding host-pathogen interactions with a particular focus on innate immune responses. We apply omics approaches to dissect these interactions, performing in vivo profiling and building in vitro systems to define host-pathogen interactions. We have a particular passion for understanding the mechanisms by which NK cells recognize and respond to pathogens. We currently have projects evaluating immunity to SARS-CoV-2, HIV, influenza, and tuberculosis.

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

Dr. Luby’s research group is engaged in several efforts to generate knowledge that will alter the way that bricks are manufactured across South Asia so that they generate less air pollution, less climate change and tens of thousands fewer deaths per year. This involves: 1) evaluating interventions to improve combustion efficiency within brick kilns and so simultaneously reduce coal costs for producers while generating less pollution 2) using remote sensing to specify the location of brick kilns and ultimately evaluate their emissions.

Another strand of his work looks at the release of lead into the environment in low and middle income countries, seeks to identify the sources of lead that is generating the greatest public health burden and develops and evaluates interventions to reduce this burden.

His research group also explores practical interventions to reduce infectious disease transmission in low and middle income countries. These activities include efforts to maximize the uptake of masks, water treatment and vaccines with careful evaluation of the impact of these interventions. His research group explores strategies to reduce the risk of pathogen transmission in healthcare facilities in lower income countries.

Dr. Parsonnet is an Infectious Diseases epidemiologist and clinician.  The Parsonnet lab works to understand how infectious agents influence the development of chronic diseases.  During the COVID crisis, the lab has also been actively involved in a wide range of investigations of this disease ranging from large seroepidemiologic studies to novel treatment trials to collaborative studies on COVID immunology.  Studies that could potentially take a fellow include:

• Large seroepidemiologic, longitudinal studies of COVID in the counties throughout California both before and after the initiation of vaccines.   We have collected data sets that allow us to understand risk factors for breakthrough infections,  how vaccination and other interventions change behavior,  and the role of natural infection in building immunity.
• Studies on COVID infection, immunity and vaccination in patients receiving dialysis
• A clinical trial of camostat, a TMPPRS2 blocker, that prevents SARS-CoV2 from entering cells.
• Studies that define the normal human body temperature in children and adults
• Research on how skin care in babies varies across populations and how this influences skin integrity and development of allergic diseases later in life (with Kari Nadeau).
• Studies on the development of the pediatric virome, microbiome and immunome in the first three years of life.

Singh lab - basic and translational science for parasitic amebic pathogens including gene expression, developmental control and identification of new drug regimens.

Current Research Projects

• Pediatric Research Immune Network on SARS-CoV-2 and MIS-C (PRISM)
• Work with our team to consent subjects, obtain and process samples for immune assays to determine the immune responses in children with COVID.

• Identification and Therapeutic Targeting of a Novel Cell Population in Rejection of Vascularized Composite Allotransplantation
• Work with our microsurgeon to establish the cell populations, using CyTOF, important in the initiation of T cell‒mediated rejection of vascularized composite allotransplantation.

• Exosomes as a Reliable Noninvasive Method for Monitoring VCA Graft Rejection
• Work with our microsurgeon to assess the importance of exosomes and their cargo in graft rejection in a novel experimental model of vascularized composite allotransplantation

• Exosomes and the Immune Response in Allograft Outcomes in Pediatric Transplant
Recipients
• Work with a senior postdoctoral fellow to determine the impact of an allograft on the early post-transplant immune response.

My laboratory investigates the immune response to viruses and allogeneic tissues. We are interested in characterizing the human immune response to EBV, CMV, and SARS-CoV-2 to distinguish features that are associated with control of the virus or result in pathologies including COVID-19, MIS-C, and post-transplant viral disease. Projects that are available include 1) analysis of the diversity of TCR usage in the response to EBV, CMV, and SARS-CoV-2 through the use of next generation sequencing and single cell approaches to evaluate T cell phenotype and function; 2) characterization of the natural killer (NK) cell populations that participate in the response to viruses; 3) determining the role of the viral protein LMP1 in activation of the PI3K/Akt/mTOR pathway and the effect of targeting this pathway in EBV-associated  B cell lymphoma development. 4) identification of novel host gene targets and pathways of oncogenesis utilized by EBV.  Human immunology projects utilize cell lines as well as existing extensive repositories of  human blood and tissue samples. Animal models of transplant immunology and tumor immunology are also established in the lab.

Molecular and Cellular Immunobiology

The lab's current research is aimed primarily at understanding how hematopoietic stem cells interact with their microenvironment in order to subsequently modulate these interactions to ultimately improve bone marrow transplantation and unlock biological secrets that further enable regenerative medicine broadly. We are primarily focused on studying the cell surface receptors on hematopoietic stem/progenitor cells and bone marrow stromal cells, and are actively learning how manipulating these can alter cell state and cell fate.  We have also pioneered several antibody-based conditioning methods that are at various stages of clinical development to enable safer stem cell transplantation.

There are many exciting opportunities that stem from this work across a variety of disease states ranging from rare genetic diseases, autoimmune diseases, solid organ transplantation, microbiome and cancer. While we are primarily focused on blood and immune diseases, the expanded potential of this work is much broader and can be applied to other organ systems as well and we are very eager to develop collaborations across disease areas. The Czechowicz lab hopes to further add in the field of translation research.

Goals
We aim to increase our understanding of the basic science principles that govern these cells and then exploit these findings to develop improved therapies for patients
We are particularly focused on pediatric non-malignant bone marrow transplantation with a strong interest in genetic blood/immune diseases and bone marrow failure, but do complementry work on solid tumors with marrow disease, solid organ tolerance induction, autoimmune diseases and gene therapy/gene editing.

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 Majeti lab focuses on the molecular/genomic characterization and therapeutic targeting of leukemia stem cells in human hematologic malignancies, particularly acute myeloid leukemia (AML). In parallel, the lab also investigates normal human hematopoiesis and hematopoietic stem cells. Our lab uses experimental hematology methods, stem cell assays, genome editing, and bioinformatics to define and investigate drivers of leukemia stem cell behavior. As part of these studies, we have led the development and application of robust xenotransplantation assays for both normal and malignant human hematopoietic cells. A major focus of the lab is the investigation of pre-leukemic hematopoietic stem cells in human AML.

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.