PRISM Mentors

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.

The central focus of our laboratory is to develop novel microfluidic technologies that for high-throughput and quantitative biophysics, biochemistry, and single-cell biology.

My professional focus has been on developing a thriving and supportive research group in which the next generation of interdisciplinary scientists are trained to tackle long-standing and newly emerging questions in virology.  Our research has been driven towards elucidation of molecular mechanisms of viral replication and the development of new strategies to combat viral pathogens. A unifying theme in my work has been the use of new tools to explore questions in virology that have been inaccessible using conventional methods. My recent research efforts have centered on two significant problems: first, addressing the challenges that limit our current arsenal of antivirals by developing novel, first-in-class small molecules; and second, understanding the specificity and function of host lipids in RNA virus replication.

Throughout the decades, our team has dedicated to the conducts of innovative clinical trials and ocular imaging studies aimed to enhance our knowledge while bringing new therapeutic options for retinal vascular diseases, including age-related macular degeneration, diabetic retinopathy and diabetic macular edema, retinal vein occlusion and vaso-occlusive diseases, retinal degeneration as well as uveitic and ocular inflammatory diseases. Our efforts, often started with first-in-human trials, have led to the availability of VEGF-antagonists such as ranibizumab and aflibercept, interleukin inhibitors such as tocilizumab and sarilumab, and mTOR inhibitors such as sirolimus for many patients throughout the world. We have developed and perfected approaches to plan and execute effectively and economically multi-centered investigator-sponsored trials. We have also established teams that receive, process, and grade ocular images of the anterior and posterior segments and teams that coordinate the successful conducts of studies. Medical students, residents, fellows, and faculty members from around the globe, near and far, have joined our team to pursue our mission in enhancing the knowledge, diagnosis, and management of retinal and uveitic diseases through clinical research to preserve and improve vision for our patients. We are committed to the success of every team member.

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

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/

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.

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.

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.

The Frock laboratory is interested in elucidating mechanisms of DNA double-stranded break (DSB) repair and chromosome translocations.  We employ a high-throughput sequencing technology that identifies and maps cellular DSBs.  We are interested in further developing this technology to more fully quantify the DSB repair fates from targeted DSBs.  Our research disciplines are broad and cover aspects of molecular and cancer biology, bioinformatics. immunology, genome editing, and radiation biology.

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.

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.

The Hernandez-Lopez Lab works at the interface of mechanistic, synthetic, and systems biology to understand and program cellular recognition, communication, and organization. We are currently interested in engineering biomedical relevant cellular behaviors for cancer immunotherapy. We are also launching new multidisciplinary projects.

We are looking for outstanding, motivated graduate students and physician-scientists from diverse fields who are interested in joining our interdisciplinary research program. Postdoctoral candidates with expertise (or an interest in learning) preclinical animal models of disease or structural biology (cryo-EM) are particularly encouraged.

Roger has broad interests in particle astrophysics and cosmology. Roger and his group are currently working on studies of gravitational lensing, compact objects (black holes, neutron stars and white dwarfs) and cosmic rays, tackling difficult questions such as the unknown nature of the gamma-ray flares of the Crab Nebula. He is interested in topics which range from pure theory through phenomenological studies to analysis of observational data. Some of his groups research is strongly computational but plenty is not.

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.

The Kopito laboratory seeks a molecular understanding of how cells maintain the fidelity of their proteomes. Unlike DNA, which can be repaired if damaged or incorrectly made, proteins cannot be mended. Instead, damaged or incorrectly synthesized proteins must be rapidly and efficiently destroyed lest they form toxic aggregates. Our laboratory use state-of-the-art cell biological, genetic and systems-level approaches to understand how proteins are correctly synthesized, folded and assembled in the mammalian secretory pathway, how errors in this process are detected and how abnormal proteins are destroyed by the ubiquitin-proteasome system.

The Kopito laboratory seeks a molecular understanding of how cells maintain the fidelity of their proteomes. Unlike DNA, which can be repaired if damaged or incorrectly made, proteins cannot be mended. Instead, damaged or incorrectly synthesized proteins must be rapidly and efficiently destroyed lest they form toxic aggregates. Our laboratory use state-of-the-art cell biological, genetic and systems-level approaches to understand how proteins are correctly synthesized, folded and assembled in the mammalian secretory pathway, how errors in this process are detected and how abnormal proteins are destroyed by the ubiquitin-proteasome system.

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

My lab is focused on the development of imaging and molecular biomarkers for precision cancer medicine. We are interested in a broad range of clinical applications, including early cancer detection, diagnosis, prognostication, and prediction of treatment response. To achieve this goal, we integrate and analyze large-scale patient data sets with clinical annotations, including both imaging (radiologic, histopathologic) and molecular (genomic, epigenomic, transcriptomic) data. In addition, we develop and apply novel statistical and machine learning methods. We are a multidisciplinary team with a diverse background and yet converging theme. Our ultimate goal is to clinically translate novel biomarkers to guide selection of optimal therapy and improve outcomes for cancer patients.

Our lab uses the tools of cognitive neuroscience to understand how decision making, executive control, and learning and memory are implemented in the human brain.  We also develop neuroinformatics tools and resources to help researchers make better sense of data and to do research that is more transparent and reproducible.

Lab overview

The communication between cells and their environment depends on a finely tuned decoding of extracellular cues into an array of intracellular signaling cascades that drive a cellular response. These signals are integrated through highly dynamic and context specific signaling networks that collectively define the phenotypic output. Given the complexity and dynamic state of signaling networks, the current understanding of their constituents and how they are spatiotemporally regulated in the cell as a result of a specific input is incomplete.

The Huttenhain lab studies mechanisms of intracellular signal integration through G protein-coupled receptors (GPCRs) by employing an interdisciplinary approach to probe, model, and predict how signaling network dynamics translate extracellular cues into specific phenotypic outputs. GPCRs represent the largest family of membrane receptors and mediate most of our physiological responses to hormones, neurotransmitters and environmental stimulants.  Developing quantitative proteomics approaches to capture the spatiotemporal organization of signaling networks and combining these with functional genomics to study their impact on physiology, we aim to better understand GPCR signaling and to provide a solid foundation for the design and testing of novel therapeutics targeting GPCRs with higher specificity and efficacy.

Relevant publications

• Lobingier B, Hüttenhain R, Eichel K, Ting AY, Miller KB, von Zastrow M, Krogan NJ. (2017) An approach to spatiotemporally resolve protein interaction networks in living cells. Cell 169, 350-360. PMC5616215.
• Polacco BJ, Lobingier BT, Blythe EE, Abreu N, Xu J, Li Q, Naing ZZC, Shoichet BK, Levitz J, Krogan NJ, Von Zastrow M, Hüttenhain R. (2022) Profiling the diversity of agonist-selective effects on the proximal proteome environment of G protein-coupled receptors. bioRxiv 2022.03.28.486115
• Zhong X, Li Q, Polacco BJ, Patil T, DiBerto JF, Vartak R, Xu J, Marley A, Foussard H, Roth BL, Eckhardt M, Von Zastrow M, Krogan NJ, Hüttenhain R. (2023) An automated proximity proteomics pipeline for subcellular proteome and protein interaction mapping. bioRxiv 2023.04.11.536358
   

The investigative interests of my lab falls within the general themes of

1) Developing precision diagnostics for infectious diseases that integrates pathogen, host, and drug response information. This includes

• Developing high-content, near-patient, diagnostic system for rapid broad pathogen detection and characterization.
• Integrating multi-omics molecular and phenotypic data layers with novel computational approaches into advanced diagnostics and predictive analytics for acute infections.
• Developing personalized, rapid antimicrobial susceptibility analysis system based on early response kinetics in physiological conditions to inform antimicrobial choice, dosage, and duration.
• Exploring the clinical utility of serum bactericidal assay as a humoral immune functional assessment in the prediction of bloodstream infections. 

2) Understanding the functional roles of extracellular DNA in neutrophil extracellular traps and biofilm

• As a DNAzyme that drives bactericidal effects and immunopathologies. 

Water resources planning under uncertainty

We work to advance water resources management to promote resilient and equitable responses to an uncertain future. We develop computational modeling approaches that bridge the natural, built, and social environments. Our approach improves understanding of the water and climate risks that threaten people and the environment, while developing systems-based engineering and policy solutions.

Heilshorn's interests include biomaterials in regenerative medicine, engineered proteins with novel assembly properties, microfluidics and photolithography of proteins, and synthesis of materials to influence stem cell differentiation. Current projects include tissue engineering for spinal cord and blood vessel regeneration, designing injectable materials for use in stem cell therapies, and the design of biomaterials for culture of patient-derived biopsies and organoids. Postdoctoral candidates with expertise (or an interest in learning) preclinical animal models of injury and disease are particularly encouraged.

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