PRISM Mentors

My work focuses on understanding the genomic and proteomic profiles of different sources of MSCs and their derived EVs, developing novel strategies to deliver and home these MSC-based therapies to target tissues, using focused ultrasound to optimize the injured tissue microenvironment for these therapies and then imaging the biodistribution of MSCs with novel imaging probes. By translating stem cell therapies into patients using minimally invasive strategies, his team is leading the efforts in a new emerging field called “Interventional Regenerative Medicine (IRM)”. In addition, his team has been developing multi-functional bioscaffolds and nanoplatforms to facilitate the clinical translation of different cellular therapies.

Department URL:
https://med.stanford.edu/radiology.html

My lab is an interdisciplinary group spanning medical physics and technology development, basic cancer and radiation biology, and preclinical and clinical imaging.

The two main programs are:

1. Development of next-generation medical linear accelerator technology for delivery of ultra-rapid FLASH radiation therapy for cancer, working closely with collaborators at SLAC National Accelerator Laboratory. We are currently designing and building a system for preclinical FLASH research in small animal models. Using the same platform technologies, we are also laying the groundwork for a clinical treatment system (PHASER) for FLASH radiation therapy for general cancer therapy in human patients, with a focus on compact, economical, and clinically efficient design.

2. Fundamental radiation biology research in ultra-rapid FLASH radiation therapy in small animal and in vitro models. We are investigating the biological mechanisms underlying the observed therapeutic index of FLASH, producing less normal tissue radiation injury and simultaneously equal or increased tumor killing compared to conventional dose rate irradiation. We are investigating physical, radiochemical, immunological, vascular, and other microenvironmental aspects in multiple model systems.

Flatworms include more than 44,000 parasites, many of which are pathogenic to humans or livestock, with flukes, tapeworms, and hookworms as notorious representative species. They typically transmit through multiple hosts using several drastically different body plans specialized for infecting and reproducing within each host. Although flatworms’ complex life cycles were established over a century ago, little is known about the cells and genes they use to optimize their transmission potential, thereby limiting our ability to develop effective therapeutic and preventive strategies. We aim to develop a comprehensive cellular and molecular understanding of the stereotypical life cycle of a blood fluke, Schistosoma mansoni, and identify novel targets to block it. Schistosomes cause one of the most prevalent but neglected infectious diseases, schistosomiasis. With over 250 million people infected and a further 800 million at risk of infection, schistosomiasis imposes a global socioeconomic burden comparable to that of tuberculosis, HIV/AIDS, and malaria. This project will use novel single-cell technologies to build a schistosome "cell atlas", and map the developmental states of their stem cells as they produce all other cell types in the schistosome body plans.

Glia are a frontier of neuroscience, and overwhelming evidence from the last decade shows that they are essential regulators of all aspects of the nervous system. The Zuchero Lab aims to uncover how glial cells regulate neural development and how their dysfunction contributes to diseases like multiple sclerosis (MS) and in injuries like stroke.

Although glia represent more than half of the cells in the human brain, fundamental questions remain to be answered. How do glia develop their highly specialized morphologies and interact with neurons to powerfully control form and function of the nervous system? How is this disrupted in neurodegenerative diseases and after injury? By bringing cutting-edge cell biology techniques to the study of glia, we aim to uncover how glia help sculpt and regulate the nervous system and test their potential as novel, untapped therapeutic targets for disease and injury.

We are particularly interested in myelin, the insulating sheath around neuronal axons that is lost in diseases like MS. How do oligodendrocytes- the glial cell that produces myelin in the central nervous system- form and remodel myelin, and why do they fail to regenerate myelin in disease? Our current projects aim to use cell biology and neuroscience approaches to answer these fundamental questions. Ultimately we hope our work will lead to much-needed therapies to promote remyelination in patients.

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.

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

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

The Gifford lab is focused on defining the complex genetic and molecular mechanisms that are necessary for faithful cardiovascular development and how perturbation of these mechanisms can lead to disease. We use both stem cell and rodent experimental models to:

• characterize the cellular interactions involved in cardiovascular development
• define the oligogenic mechanisms underlying congenital heart diseases, such as hypoplastic left heart syndrome and left ventricular noncompaction
• explore the link between congenital heart disease and neurodevelopmental delay

We also collaborate closely with clinicians, for example on a project integrating cardiac imaging and genetic data to predict adverse cardiac outcomes. Ultimately, we hope to make personalized medicine a reality for those that suffer from CHD and associated comorbidities, such as autism.

Research in this laboratory focuses on problems where deep insights into enzymology and metabolism can be harnessed to improve human health.
For the past two decades, we have studied and engineered enzymatic assembly lines called polyketide synthases that catalyze the biosynthesis of structurally complex and medicinally fascinating antibiotics in bacteria. An example of such an assembly line is found in the erythromycin biosynthetic pathway. Our current focus is on understanding the structure and mechanism of this polyketide synthase. At the same time, we are developing methods to decode the vast and growing number of orphan polyketide assembly lines in the sequence databases.

For more than a decade, we have also investigated the pathogenesis of celiac disease, an autoimmune disorder of the small intestine, with the goal of discovering therapies and related management tools for this widespread but overlooked disease. Ongoing efforts focus on understanding the pivotal role of transglutaminase 2 in triggering the inflammatory response to dietary gluten in the celiac intestine.

My research interests lie at the interface between chemistry and biology. While ongoing research in my lab focuses on multiple problems, all of these efforts are motivated by the twin goals of shining light on fundamentally new molecular mechanisms in biology and leveraging these insights to address unmet challenges in human health. Two examples of ongoing research themes in my lab are outlined below:

I] Assembly-line biosynthesis of polyketide antibiotics: The primary objective of this longstanding research project in my lab is to understand the enzymatic mechanisms of assembly-line polyketide synthases (PKSs). Having defined the physical boundaries and chemical reactivity of individual domains and modules, our goal now is to understand these assembly lines as integrated metabolic systems. We also seek to understand the genetic mechanisms for extraordinary evolutionary diversification of this family of multifunctional enzymes.

II] Chemical approaches to understanding celiac disease pathogenesis: Over the past two decades, we have made significant contributions to an understanding of celiac disease (CeD) pathogenesis. Furthermore, at each step along the way, we have sought to translate these emerging molecular insights into enhanced disease management tools for CeD patients and their doctors, as illustrated by the translation of two experimental therapeutics from our lab into advanced preclinical/early clinical studies, and the translation of a biomarker discovered in our lab into CeD patients.
 

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.

Our group's research interests center around entrepreneurship. We are particularly interested in policy and the institutional environment, entrepreneurs in emerging economies and entrepreneurship among historically under-represented populations. We also do some work on technology platforms to facilitate startups and refugee entrepreneurship.

Our lab is interested in the capability of robots and other agents to develop broadly intelligent behavior through learning and interaction. We work on robotics and machine learning, and we are affiliated with SAIL, the ML Group, the Stanford Robotics Center, and CRFM.

The Jacobs-Wagner lab has two main research interests:

1. They examine the general principles and spatiotemporal mechanisms by which bacterial cells replicate. Bacteria are infamous for their remarkable ability to proliferate. Yet, despite their medical and agricultural importance, little is known about how bacteria control and integrate their growth, cell morphogenesis and cell cycle functions. The Jacobs-Wagner lab addresses this fundamental question at all levels, from a systems-level perspective down to the physical mechanisms, using genetics and cutting-edge quantitative microscopy techniques. The primary model bacterial systems are Escherichia coli and Caulobacter crescentus. Microbiologists, physicists and individuals with expertise in quantitative biology are encouraged to contact us.
2. Recently, the Jacobs-Wagner lab expanded their interests to the Lyme disease agent Borrelia burgdorferi, revealing unsuspected ways by which this pathogen grows and causes disease. Lyme disease is tick-born disease whose incidence and geographic distribution have rapidly increased over the years, in part due to climate change. The Jacobs-Wagner lab has developed genetic and cell biological tools as well as mass spectrometry and microscopy protocols to study this important human pathogen, from its unique cell biology to its pathogenesis. Individuals with expertise in microbial pathogenesis or immunology are encouraged to contact us.
    

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

We combine biophysical methods with in vivo approaches to understand how viruses such as HIV and SARS-CoV-2 infect host cells and elicit specific humoral immune responses. Our research will translate knowledge of the structural correlates of antibody-mediated neutralization of viruses into the rational development of highly protective antibodies. A related goal is the structure-based design of potent and stable immunogens for vaccination.

My research focuses on the influence of the external environment on entrepreneurship. Specifically, I have sought to be a leader in investigating the types of environments that encourage the founding of high growth, technology-based firms. Although I build on previous work that focuses on individual characteristics, network ties, and strategy, my major contribution is to demonstrate that institutions matter. I have broken new ground in showing that effective institutional change influences who starts firms, not just how many firms are started. I have repeatedly studied entrepreneurship in a single country (China, Chile, Japan, and the U.S.) before and after a major institutional change. My work is divided into three streams: (1) formal institutions (policies and regulations), (2) university and industry environments, and (3) informal institutions (social movements).
STREAM 1: My research in this stream advances theory by introducing novel mechanisms (e.g. barriers to growth and failure, institutional inconsistency), introducing new concepts (e.g. skill adequacy and context relevance) and in theorizing that institutional changes that lower barriers to growth and to failure alter who becomes an entrepreneur, the type of firms, and performance.
STREAM 2: My work in this stream changes the way we think about team composition as well as what characteristics lead to venture performance by linking their impacts to industry environments.
STREAM 3: In this stream, I explored how social movement organizations can change firms.
My research changes the way we think about how the environment – formal institutions, informal institutions, and industry contexts – influences entrepreneurship. I am a leader in situating ventures within environments and showing that interactions between environments and entrepreneurs matter. I am among the first to argue and show that policies that foster high-growth entrepreneurship are different than those that spawn small businesses. If policy leaders wish to foster technology-based start-ups, then we must consider how institutions operate. My research shows that institutional changes can significantly influence the types of firms that are created, who creates them, and how they perform. My research challenges widely accepted ideas about entrepreneurship by highlighting taken-for-granted notions that are incomplete or misleading. My studies call into question the assumption that institutions that make it easier to start firms are unambiguously beneficial, and that experienced, diverse founding teams are always superior. My theoretical contributions include introducing such concepts as institutional barriers to growth, skill adequacy and context relevance. I lead the way in broadening our conception of entrepreneurship beyond the developed North American economies. I have contributed methodologically by (A) showing how to measure talent, (B) collecting data internationally, (C) using randomized field experiments, and (D) analyzing multi-industry databases with state-of-the-art statistics (instrumental variables, differences-in-differences). I have been a pioneer in overcoming the challenges of inferring causality, by finding changes that altered the landscape for entrepreneurship, along with collecting novel data in international settings. In future work, I plan to do more studies incorporating software development for data collection and digital platforms for randomized experiments focusing on issues related to strategic change and entrepreneurship training. 

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.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

I am a Theoretical Physicist by training and have been working on mathematical and computational modeling of biological systems since my PhD. My lab studies hearing and balance systems and is interested in how sensory signals are filtered, transduced, amplified, and transmitted to the brain. We have worked on the ear's mechanics, synaptic dynamics, and otoacoustic emissions and use experimental data to motivate and test our mathematical models. In collaborations with several experimental labs, we have helped explain their data and tested our mathematical models. Our work is highly interdisciplinary and sits at the intersection of many fields including physics, biology, mathematics, neuroscience, and engineering. At present, we are focusing on the sensory cells in hearing and balance systems and on auditory evoked potentials.

To understand biology, we need chemistry and physics as the physical and chemical properties of biomolecules enable and constrain what biology can do and how it has evolved. We are particularly interested in questions of: (i) how enzymes work; (ii) how RNA folds; (iii) how proteins recognize RNA; (iv) RNA/protein interactions in regulation and control; and (v) the evolution of molecules and molecular interactions. Our interdisciplinary approaches span and integrate physics, chemistry and biology, employ a wide range of techniques, and are question driven. We have new projects in each of the above areas as we:
• Pioneer high-throughput quantitative approaches to study enzymes—to address how an entire protein contributes to its function, how allosteric signals are propagated, how different human alleles affect function and/or stability, and ultimately how to design new enzymes (with Polly Fordyce);
• Work to understand the evolution of enzyme function and stability via functional, genome-scale analyses, and experimental evolutionary studies;
• Pioneer the determination of enzyme conformational ensembles—and linking these to function via novel “ensemble¬–function” studies;
• Develop a quantitative and predictive model for RNA tertiary folding thermodynamics and kinetics, building from the “RNA Reconstitution Model”;
• Provide the first quantitative and complete descriptions of the affinity and specificity of RNA binding proteins for all possible RNA sequences and structures (with Will Greenleaf);
• Pioneer Quantitative Cellular Biochemistry (QCB) to bring together the power of biochemistry and genomics to the study molecular interactions and function in cells, with the goal of providing quantitative and predictive models for molecular function and regulation in cells.

Protein self-assembly in evolution, disease, and development; Systems biology of aging;  Mutational robustness in cancer and pathogens; Quantitative analysis of evolving genotype-to-phenotoype maps. Epigenetic control of interspecies interactions.

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