PRISM Mentors

My research program aims to understand the cellular and molecular mechanisms that underlie synapse function during behavior in the developing and mature brain, and how synapse function is altered in neurodevelopmental disorders. Within this broad research area, I am specifically interested in the following three overall themes.
1. Investigate the synaptic signaling mechanisms regulating homeostatic synaptic plasticity, the role of postsynaptic protein translation in this control, and how these signaling mechanisms are compromised in neurodevelopmental disorders. Toward this goal, we combine molecular, biochemical, electrophysiological, and cell biological approaches to examine retinoic acid signaling pathways that mediate activity-dependent regulation of synaptic function, both globally at a whole cell level or locally with each synapse as an independent computational unit of the neuron. We also explore how genetic mutations implicated in neurodevelopmental disorders alter homeostatic synaptic plasticity in both mouse models and human neurons derived from patient iPS cells.
2. Investigate interactions between retinoic acid-mediated homeostatic synaptic plasticity and other forms of long-lasting synaptic changes (e.g. Hebbian plasticity), how this interaction impacts learning and memory formation at behavioral levels, and how defective homeostatic synaptic plasticity underlies cognitive deficits in neurodevelopmental disorders. Our investigation of molecular mechanisms underlying homeostatic synaptic plasticity provides unique molecular tools with which we could begin to manipulate homeostatic plasticity specifically and examine its impact on Hebbian plasticity. We use both behavioral assays and slice electrophysiology as our functional readouts. Moreover, we developed protocols to investigate memory recall accuracy using activity-dependent genetic labeling in behaving animals, thus further exploring the mechanisms of memory encoding (or lack thereof in the case of disease models) at neural network levels.
3. Investigate synaptic and circuit changes in spinal dorsal horn in peripheral nerve injury-induced neuropathic pain models. We extend our investigations of synaptic plasticity mechanisms from the brain circuits to spinal dorsal horn circuits because we believe some of the most fundamental molecular mechanisms underlying experience-dependent synaptic modifications are shared between similar types of synapses in different regions of the CNS. Indeed, our recent work on synaptic changes driving nerve injury-induced spinal disinhibition supports this notion. The current application builds upon ample preliminary data and applies knowledge generated from our studies in the brain circuits to explore spinal circuits. 
To achieve these goals, we combine expertise spanning molecular and cellular biology, protein biochemistry, stem cell biology, slice electrophysiology, in vivo imaging and MEA recordings, and behavioral assays.

We seek greater understanding of the genetic and epigenetic mechanisms driving tumorigenesis and disease progression in malignant brain tumors. We currently study the capacity of cellular and cell-free nucleic acids to inform treatment choices in patients with brain tumors, mechanisms of brain tumor cell migration, and identify potentially targetable genes and pathways. Our laboratory space lies at the heart of the Stanford campus between the core campus and the medical facilities, emblematic of the translational aspects of our work.

THE PETRITSCH BRAIN TUMOR STEM CELL AND MODELS RESEARCH LAB

The Petritsch lab broadly investigates underlying causes for the intra-tumoral heterogeneity and immune suppression in brain tumors from a developmental neurobiology point of view. Defects in cell fate control could explain many key defects present in brain tumors and an understanding of how brain cells control the fate of their progeny may identify novel points of vulnerabilities to target with therapeutics. Of special emphasis, we study the establishment of cell fates within normal hierarchical brain lineages for comparison to the dysregulated cell-fate hierarchies seen in brain tumors. Our lab was the first to demonstrate that normal adult oligodendrocyte progenitor cells (OPCs) undergo asymmetric divisions to make cell fate decisions, i.e. to generate OPCs as well as differentiating cells each time they divide. Drawing from these data, we investigate whether brain tumors divide along hierarchical lineages and how oncogenic mutations might affect cell fate decisions within these hierarchies. A major line of investigation in our lab focuses on whether defects in the asymmetric division lead to aberrant cell fate decisions that cause the paradigm mixed-lineage phenotypes and the intra-tumoral heterogeneity present across tumors.

To study the interactions between tumor cells and the immune system, we have developed and utilized transplantable mouse glioma models. We are tasked to facilitate and coordinate the distribution of fresh tissue from the neurosurgery operating room and have access to fresh brain tissue from patient surgeries, from which we prepare cell culture models for brain tumors and normal progenitors. We complement our work with human cells with studies in genetically engineered mouse models of gliomagenesis to conduct molecular, cellular, and bioinformatic analyses.

We study the roles of microRNAs in cortical projection neuron development, with an emphasis on corticospinal motor neurons. We have identified a group of mircoRNAs specifically enriched in corticospinal motor neurons during their development and are investigating their functions in cortical progenitors in vitro and in vivo, as well as in ES cells.

Dr. Bhalla received his training in molecular biology at UC San Francisco. His postdoctoral work centered on the regulation of aldosterone-mediated sodium transport in health and disease. In his laboratory he uses both in vitro and in vivo approaches for several projects related to the role of the kidney in health, diabetes, and hypertension. (1) Diabetic kidney disease is costly and consequential. Diabetic kidney disease is the most common form of chronic kidney disease in the world, yet no curative therapy is available. Studies of the susceptibility of diabetic kidney disease led to the discovery of differential regulation of endothelial-specific molecule-1, Esm-1 (endocan) in susceptible strains of mice. Esm-1 is a secreted proteoglycan that is enriched in glomerular endothelium and inhibits interferon signaling in glomeruli in the setting of diabetes and other inflammatory diseases. Ongoing rescue and deletion experiments explore the role of Esm-1 in diabetes and diabetic kidney disease. We also study the regulation of Esm-1 transcription and protein stability. (2) Investigation of the mechanisms of hypertension in the setting of obesity and insulin resistance using renal tubular epithelial insulin receptor deletion challenged the role of insulin in the hypertension of obesity, insulin resistance, and the metabolic syndrome. These studies also shed light on the role of insulin in control of glucose reabsorption via SGLT2. Ongoing studies focus on molecular mechanisms of insulin-regulated SGLT2 and its contrast with insulin resistant pathways in other cell types and tissues. (3) Inhibition of sodium reabsorption using diuretics is a mainstay of therapy for hypertension and edema-forming states. Study on the consequences of diuretic therapy using tubular morphometry and single cell approaches have led to additional work on mechanisms of tubular remodeling in vivo.

The overall theme of our research has been the genetic basis of cardiovascular disease across the continuum from Discovery to the development of Model Systems to the Translation of these findings to the clinic and most recently to the Public Health aspect of genetics. Currently our Discovery and basic translational efforts center on understanding the genetic basis of insulin resistance using genome wide association studies coupled advanced genetic analyses such as colocalization with exploration using in vitro and in vivo model systems including induced pluripotent stem cells and and gene editing screens. 

The Cardiovascular Biomechanics Computation Lab  develops fundamental computational methods for the study of cardiovascular disease progression, surgical methods, treatment planning and medical devices.  We focus on patient-specific modeling in pediatric and congenital heart disease, as well as adult cardiovascular disease.  Our lab bridges engineering and medicine through the departments of Pediatrics, Bioengineering, and the Institute for Computational and Mathematical Engineering. We develop the SimVascular open source project.

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.

A central focus of our laboratory is to uncover new regulatory mechanisms in cell-cell communication system, understand how these mechanisms are damaged in disease states and devise strategies to repair their function. We are actively recruiting post-doctoral fellows to join projects in the following areas:
--Signaling pathways implicated in birth defects, cancer and regeneration.
--Regulation of signaling and development by primary cilia.
--Genetic and biochemical dissection of lipid pathways that regulate signaling, development and cancer.
--The role of biomolecular condensates in cancer and cancer therapeutics.
We strive to provide a supportive, inclusive, organized and collaborative lab environment that maximizes the ability to tackle important biomedical problems. Career development is a priority. Nearly all prior lab members have obtained multiple publications and top-level competitive positions in academics or in the biotech industry.

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

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.

The Cardiovascular Biomechanics Computation Lab  develops fundamental computational methods for the study of cardiovascular disease progression, surgical methods, treatment planning and medical devices.  We focus on patient-specific modeling in pediatric and congenital heart disease, as well as adult cardiovascular disease.  Our lab bridges engineering and medicine through the departments of Pediatrics, Bioengineering, and the Institute for Computational and Mathematical Engineering. We develop the SimVascular open source project.

Our research focuses on the control of immune responses to alloantigen and viruses (EBV, SARS-CoV-2) using both experimental models and human immunology. Current studies ongoing in the lab are:

Insight into Development and Progression of Multi-System Inflammatory Syndrome and  COVID in Children.
Exosomes and microRNAs in the regulation of  Immune Responses
NK Cell Diversity and Responses to viral and allo antigens
Novel T regulatory populations

Molecular and Cellular Immunobiology/CyTOF/bioinformatics