PRISM Mentors

The main focus of Dr. Gomez-Ospina’s lab is to develop therapies for patients with genetic neurodgenerative diseases. The lab uses genome editing and stem cells to produce definitive treatments for childhood neurodegenerative diseases, many of which are lysosomal storage disorders.

Current projects in the lab include developing autologous transplantation of genome-edited hematopoietic stem cells for Mucopolysaccharidosis type I, Gaucher, Krabbe disease, Frontotemporal Dementia, and Friedreich's ataxia.

Although there is a strong translational focus to the lab, we are also pursuing basic science questions to understand and enhance our therapies including: 1) increasing the efficiency of genome editing tools, 2) understanding microglia turnover in response to conditioning before hematopoietic stem transplant, and 3) stablishing brain-specific conditioning regimens to neurometabolic diseases.

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.

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.

Our group works with  adaptive optics - optical systems that correct for aberrations using mirrors that change their shape thousands of times per second. This can allow telescopes located on the Earth to correct for atmospheric turbulence and produce diffraction-limited images, which we use to study giant extrasolar planets through direct imaging with the Gemini Planet Imager (GPI) instrument. Direct imaging of extrasolar planets separates the light of the (faint) planet and (bright) star, allowing us to measure the spectrum of young self-luminous giant exoplanets. We are currently planning an upgrade to GPI, adding a faster adaptive optics system using predictive control, and more accurate wavefront sensors. 
 
We are studying this technology for more powerful instruments on the ground and space. We are also exploring applications in biology - microscopes that can look into tissues.

Aaron's current research focus is the study of dark energy using images from the ongoing Dark Energy Survey (DES) and the  future Large Synoptic Survey Telescope (LSST). He is interested in studying dark energy using both galaxy clusters and weak gravitational lensing. His research group connects instrumental work, in particular active optics and wavefront measurements at DES and a program of camera-wide testing at LSST,  with cosmology measurements. For example, they are developing a new method to characterize the telescope+camera point spread function using optical data, to be part of the weak lensing data analysis at both DES and LSST.

Together with Dan Akerib, Tom 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 atSLAC 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.

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.

Our lab focuses on the biology of chimeric antigen receptor (CAR) T cells in order to improve the efficacy and safety of this therapy (1) by investigating donor and third-party CAR T cells in an immunocompetent mouse model of allogeneic hematopoietic cell transplant (allo-HCT) and (2) by assessing the impact of the intestinal microbiome on CAR T cell response. We will seek to enhance the development, administration, and mechanistic understanding of how to safely administer donor and third-party CAR T cells with the aim to potentially translate our work to the clinic. We will investigate the regulatory mechanism of the impact of bacterial taxa and the metabolites that they produce on CAR T cell outcomes.

As a physician scientist with a clinical focus on osteoporosis, my laboratory focuses on stem cell sources for bone-forming osteoblasts, and osteoblast support of hematopoiesis in the bone marrow. In particular we are interested in the pathways that promote osteoblast differentiation, using genetically modified mice and lineage tracing techniques in vivo. We are also studying the role of the osteoblast niche in normal hematopoiesis and bone metastases from breast cancer.

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

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. 

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.

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.

Stanford Solutions Science Lab.

The Stanford Solutions Science Lab designs solutions to improve health and well-being of children, families, and the planet.  Dr. Robinson originated the solution-oriented research paradigm. He is known for his pioneering obesity prevention and treatment research, including the concept of stealth interventions. His research applies social cognitive models of behavior change to behavioral, social, environmental and policy interventions for children and families in real world settings, making the results relevant for informing clinical and public health practice and policy. His research is largely experimental, conducting rigorous school-, family- and community-based randomized controlled trials. He studies obesity and disordered eating, nutrition, physical activity/inactivity and sedentary behavior, the effects of television and other screen time, adolescent smoking, aggressive behavior, consumerism, and behaviors to promote environmental sustainability. Rich longitudinal datasets of physical, physiological, psychological, behavioral, social, behavioral, and multi-omics measures are available from our many community-based obesity prevention and treatment trials in low-income and racial/ethnic minority populations of children and adolescents and their parents.

Stanford Screenomics Lab - Human Screenome Project.

People increasingly live their lives through smartphones. Our Stanford Screenomics app captures everything that people see and do on their smartphone screens – a record of digital life – by taking a screenshot every 5 seconds. The resulting sequence of screenshots, make up an individual’s screenome, an unique and dynamic sequence of exposures, thoughts, feelings, and actions. To date, we have collected more than 350 million screenshots from 6-12 months of phone use from national samples of about 500 hundred adults and adolescents and their parents. Opportunities available to study the screenome to understand digital media use and its impacts on health and behavior,  develop novel diagnostics and prognostics from the screenome, and deliver precision interventions to improve health and well being. An opportunity to help build this paradigm-disrupting new science.

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

The Weker Research Group is at the Stanford Synchrotron Radiation Lightsource (SSRL), a Directorate of the SLAC National Accelerator Laboratory. SLAC is a Department of Energy National Lab managed by Stanford Univeristy. Our research is focused on X-ray microscopy and X-ray characterization of materials far from equilibrium. Using X-rays we study a broad range of systems including energy storage materials such as Li-ion batteries, catalysts, and 3D metal printing (additive manufacturing). 

Our group at SLAC National Accelerator Laboratory is leading R&D of machine learning applications for in the area of experimental neutrino physics and a wider community of High Energy Physics.  Modern neutrino experiments employ a big (100 to 10,000 tonnes), high-resolution (~mm/pixel) particle imaging detectors that records meters-long particle trajectories produced from a neutrino interaction. We address fundamental challenges in modeling these detectors, analyzing particle images, and inferring physics from big data using machine learning and advanced computing techniques. Our research has potential to accelerate physics discovery process by orders of magnitude and to maximize physics information extracted from the big, high-recision particle imaging detectors. 

Areas of technical R&D include:

• Development and optimization of end-to-end deep-learning based data analysis chain
• Scaling applications at massively parallel computing infrastructure
• Quantification of uncertainty/confidence-interval for deep-learning models
• Mitigation and quantification of domain shift (e.g. discrepancies between data and simulation)
• Differentiable software for modeling physics and solving the inverse problems

Areas of physics research include:

• Neutrino oscillation analysis and cross-section measurements at the Short Baseline Neutrino program and Deep Underground Neutrino Experiment
• Physics of neutrino-nucleus interaction including modeling of many-body interactions inside a large (~40 nucleons) nucleus
• Modeling of detector physics processes using machine learning and differentiable simulation softwares

For details, feel free to contact Kazuhiro Terao.

Dr. Sarangi is a senior scientist at Stanford Synchrotron Radiation Lightsource (SSRL) at SLAC National Accelerator Laboratory with 19 years of experience in the application of a combination of hard and soft x-ray spectroscopic techniques to a range of systems, from complex biological/biomimetic catalysts to related homogenous catalyst systems. One of her main research foci is understanding the mechanism of first row transition metal metalloenzyme active sites involved in redox catalysis. She drives the technological development on several x-ray spectroscopy facilities and plays a critical role in training and dissemination of synchrotron-based techniques. She is also involved in strategic planning to enhance access of various research user communities to SSRL facilities.