PRISM Mentors

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.

Tom's current research focuses on studying the formation and evolution of galaxies with new numerical techniques, however, he enjoys all areas of non-linear physics which can be addressed using supercomputer calculations! His research interests span dark matter dynamics, the physics of collisionless shocks, investigating the role that cosmic rays and magnetic fields play in the formation and evolution of galaxies, modeling the formation of stars and black holes as well as turbulence, and applications of numerical general relativity.

Steve is interested in the physics of the most massive objects in the Universe and how we can use them to probe how the Universe evolved. Steve and his group are currently focused on understanding the astrophysics of galaxies and of galaxy clusters using multi-wavelength observations, and on using large, statistical samples of these objects to probe the natures of dark matter, dark energy and fundamental physics. More information regarding ongoing research and a list of Steve's current group members can be found here.

Pat and her research group are currently working hard as part of the exciting Large Synoptic Survey Telescope Dark Energy Science Collaboration in the general area of gravitational lensing. Her group is using analytic calculations, simulations and existing astronomical images to thoroughly understand potential systematic biases and challenges in extracting accurate and precise measurements of cosmic shear from gravitational lensing with current and future surveys. Current projects include the study of chromatic effects and blended objects.

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 multi-phase ISM, and the role of magnetism in star formation. These big questions demand multiwavelength observations and new data analysis techniques. Susan and her group decipher the magnetic ISM using a combination of theory and observation. Data-wise, the group uses a wide range of tracers including gas line emission and absorption, polarized dust and synchrotron emission, starlight polarization, Zeeman splitting, and Faraday rotation. Susan is involved in a number of current and future telescope projects, and leads several efforts focused on Galactic science with sensitive measurements of millimeter-wavelength emission made by cosmic microwave background experiments like the Atacama Cosmology Telescope (ACT) and the Simons Observatory (SO).

Chao-Lin’s group use the most ancient light, the Cosmic Microwave Background (CMB) radiation, emitted when the universe was in its infancy to shed light on the question of how the universe began. Currently Chao-Lin's group are involved in a number of experiments such as BICEP/BICEP2/Keck Array and have been working hard on detecting primordial B-mode polarization. His group are involved in both he design and construction of instruments as well as the data analysis and theoretical interpretation.

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.

How did the Universe form and evolve and what is it made of? Our group works on a range of topics in cosmology and astrophysics, with a focus on the formation of cosmological structure in the Universe, its impact on galaxy formation, and its use in determining the nature of dark matter and dark energy. We build and analyze numerical simulations and develop models of large scale structure and galaxy formation for comparison with large observational datasets, and develop new techniques to learn about the dark side of the Universe from these data.  We are actively involved in the ongoing Dark Energy Survey (DES), the Dark Energy Spectroscopic Instrument (DESI) and the Large Synoptic Survey Telescope (LSST), and also work on finding, measuring, and modeling dwarf galaxies with the SAGA survey.

My lab works towards developing novel therapeutics for Diabetes and Endocrine Cell Tumors. To achieve this goal, we develop (1) new animal disease models  to better understand disease pathogenesis (biologists), (2) innovative screening/discovery  platforms to identify potential therapeutic targets and lead compounds (biologists/biochemists) and  (3) synthesize new chemical entities with desired activities for therapeutic application (medicinal chemists). Hence, typical projects in the lab are interdisciplinary and collaborative where the work of biologists is supported by the power of synthetic chemistry . A major current theme in the lab is addressing the challenge   of cell-targeted drug delivery, i.e. how can we develop a medicine that only acts on the cell type of interest and apply this to (a) a regenerative therapy for diabetes and (b) the treatment of cancer.   If you're excited about disease modeling and/or drug discovery (in diabetes and cancer) my lab might be a good match for you.

Diabetes is a disorder of glucose homeostasis that causes excess hospitalization, morbidity and early mortality among the more than 34.2 million disease-affected Americans. Consequently, developing pharmacologic methods to preserve β-cell function and/or stimulate β-cell mass expansion is of intense interest. Presently, the creation of improved diabetes medications is stymied by a dearth of safe therapeutic targets. In fact, on-target but off-tissue drug effects are slowing progress across multiple diabetes therapeutic domains including β-cell regeneration, β-cell preservation, and immune-protection. In principle, stimulating the regeneration of insulin-producing β-cells could be used to restore or enhance endogenous insulin production capacity. Recently, we developed several new highly potent chemical inducers of human β-cell proliferation. However, the non-selective growth-promoting activity of these molecules prevents further clinical development. Consequently, a “modular” (readily transferable) system for β-cell-targeted drug delivery is needed to realize the next generation of diabetes therapeutics. To address this challenge, we are developing a β-cell-targeted drug delivery module based upon the uniquely high zinc content of β-cells. In this system, a zinc-chelating moiety is covalently integrated into a replication-promoting (cargo) compound to generate a bi-functional compound (βRepZnC) that selectively enhances β-cell drug accumulation and replication-promoting activity (PMID: 30527998).

We are seeking a motivated post-doctoral scholar to join our collaborative research team. This scientist will lead and engage  in developing novel βRepZnCs and uncover the biology of β-cell failure. They will define the chemical “rules” that govern zinc-dependent β-cell drug targeting,  examine the in vivo β-cell selectivity (accumulation and replication-promoting activity) of  newly developed βRepZnCs (work is supported by a synthtic chemist) and use CRISPR technology to genetically dissect the pathways that control β-cell zinc and zinc-binding drug accumulation. These studies will a break-through technology for β-cell-targeted drug delivery and provide fundamental (targetable) insights into β-cell biology. This work has the potential to transform our therapeutic approach to diabetes and provide critical insights into β-cell biology.

For the past 30 years most of my research has been focused on investigating the potential health benefits of various dietary components or food patterns, which have been explored in the context of randomized controlled trials in free-living adult populations. Some of the interventions have involved vegetarian diets, soy foods and soy food components, garlic, omega-3 fats/fish oil/flax oil, antioxidants, Ginkgo biloba, and popular weight loss diets. These trials have ranged in duration from 8 weeks to a year, with study outcomes that have included weight, blood lipids and lipoproteins, inflammatory markers, glucose, insulin, blood pressure and body composition. Most of these trials have been NIH-funded. The most impactful of these was an NIH funded weight loss diet study - DIETFITS (Diet Intervention Examining The Factors Interacting with Treatment Success) that involved randomizing 609 generally healthy, overweight/obese adults for one year to either a Healthy Low-Fat or a Healthy Low-Carb diet. The main findings were published in JAMA in 2018, and many secondary and exploratory analyses are in progress testing and generating follow-up hypotheses.

In the past few years the long-term interests of my research group have shifted to include three additional areas of inquiry. One of these is Stealth Nutrition. The central hypothesis driving this is that in order for more effective and impactful dietary improvements to be realized, public health professionals need to consider adding non-health related approaches to their strategies toolbox. Examples would be the connections between food and 1) global warming and climate change, 2) animal rights and welfare, and 3) human labor abuses (e.g., slaughterhouses, agriculture fields, fast food restaurants). An example of my ongoing research in this area is a summer Food and Farm Camp run in collaboration with the Santa Clara Unified School District since 2011. Every year ~125 kids between the ages of 5-14 years come for 1-week summer camp sessions led by Stanford undergraduates and an Education Director to tend, harvest, chop, cook, and eat vegetables...and play because it is summer camp! The objective is to study the factors influencing the behaviors and preferences that lead to maximizing vegetable consumption in kids.

A second area of interest and inquiry is institutional food. Universities, worksites, hospitals, and schools order and serve a lot of food, every day. If the choices offered are healthier, the consumption behaviors will be healthier. A key factor to success in institutional food is to make the food options "unapologetically delicious" a term I borrow from Greg Drescher, a colleague and friend at the Culinary Institute of America (the other CIA). Chefs are trained to make great tasting food, and chefs in institutional food settings can be part of the solution to improving eating behaviors. In 2015 I helped to initiate a Stanford-CIA collaboration that now ~70 universities that have agreed to collectively use their dining halls as living laboratories to study ways to maximize the synergy of taste, health and environmental sustainability (Menus of Change University Research Collaborative - MC-URC). If universities, worksites, hospitals and schools change the foods they serve, they will change the foods they order, and that kind of institutional demand can change agricultural practices - a systems-level approach to achieving healthier dietary behaviors.

The third area is diet and the microbiome. Our lab has now partnered with the world renowned lab of Drs. Justin and Erica Sonnenburg at Stanford to conduct multiple human nutrition intervention studies that involve 1) dietary intervention, 2) microbiome characterization, and 3) outcomes related to inflammation and immune function. The most impactful of these studies was the Fe-Fi-Fo study (Fermented and Fiber-rich Foods) study published in Cell in 2021. In that 10-week intervention, study participants consuming more fermented foods increased their microbial diversity and decreased blood levels in almost 20 inflammatory markers. Our ongoing Maternal and Offspring Microbiome Study (MOMS) is examining the transfer of the maternal microbiome to the infant among 132 pregnant women randomized to increase fiber, or fermented food, or both or neither for their 2nd and 3rd trimester; the infants will be tracked for 18 months.

My long-term vision in this area is to help create a world-class Stanford Food Systems Initiative and build on the idea that Stanford is uniquely positioned geographically, culturally, and academically, to address national and global crises in the areas of obesity and diabetes that are directly related to our broken food systems.

Dr. Prochaska’s research program leverages technology to study and treat tobacco, alcohol, and other risk behaviors in populations at high risk. Her research spans community-based epidemiologic studies, randomized controlled clinical trials, and health policy analysis. Dr. Prochaska has conducted and collaborated on over 25 randomized controlled behavioral intervention trials, targeting tobacco and other risk behaviors with adolescents and adults.

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.

Her lab seeks to understand the unique biological mechanisms of human placentation. While the placenta itself is one of the key characteristics for defining mammals, the human placenta is different from most available animal models: it is one of the most invasive placentas, and results in the formation of an organ comprised of cells from both the fetus and the mother. In addition to this fascinating chimerism, fetal cells are deeply involved in the remodeling of the maternal vasculature in order to redirect large volumes of maternal blood to the placenta to support the developing fetus. As such, the investigation of this human organ covers a large array of biological processes, and deals not only with understanding its endocrine function, but the physiologic process of immune tolerance, vascular remodeling, and cellular invasion.

As a physician scientist, Dr. Winn’s ultimate goal is to see this knowledge translate to improved clinical care resulting in healthier mothers and babies. Her lab uses a combination of molecular, cellular, tissue and translational studies in their research.

Utkan Demirci is a professor at Stanford University School of Medicine and serves as the interim division chief and co-director of the Canary Center for Cancer Early Detection in the Department of Radiology. His group focuses on developing innovative microfluidic biomedical technology platforms with broad applications to multiple diseases. Some of his inventions have already been translated into Food and Drug Administration-approved products serving patients. He has mentored and trained many successful scientists, entrepreneurs, and academicians. Currently, the group has a strong core focused on bio fabrication, Extracellular vesicle enrichment, and isolation, small-scale robotics for biomedicine, and the development of point-of-care metamaterial-based optical sensors.

Our research focus is in computational systems biology, primarily in cancer and more recently in neurodegenerative diseases.  We develop and apply methods to understand biological processes underlying disease, using high-throughput genomic and proteomic datasets and integrating them with phenotypes and clinical outcomes. A key interest is dissecting how the cellular composition and organization of tissues affects their behaviour in disease; and how these things might be targeted for therapy or diagnostic purposes. We collaborate with many wet lab and clinical groups at Stanford, including in the areas of cancer, immunology, and neuroscience.