PRISM Mentors

Multi-omics, multi-modal, multi-scale data fusion for precision medicine

Vast amounts of biomedical data are now routinely available for patients ranging from sequencing of tissues to liquid biopsies. In addition, new computational tools for quantitatively analyzing radiographic images are now available. Multi-scale data is now available for complex diseases at molecular, cellular and tissue scale to establish a more comprehensive view of key biological processes. Intra and inter individual heterogeneities are often quoted as the main challenge for studying complex diseases. These heterogeneities exist at all scales, from microscopic to macroscopic. We develop multi-scale modeling approach to counter heterogeneity and uncover potentially untapped synergies between different data modalities by integrating information across spatial scales. Multi-scale modeling involves linking information from molecules, cells, tissues, and organs all the way to the organism and the population. We propose to use high dimensional molecular data with tissue scale image data to develop a statistical multi-scale modeling approach in the context of multi-modal & multi-scale modeling. Such modeling can contribute toward predicting diagnosis and treatment by revealing synergies and previously unappreciated relationships. Multi-scale modeling also can contribute to a more fundamental understanding of disease development and can reveal novel insights in how data at different scales are linked to each other.

Vast amounts of molecular data characterizing the genome, epi-genome and transcriptome are becoming available for a wide range of complex disease such as cancer and neurodegenerative diseases. In addition, new computational tools for quantitatively analyzing medical and pathological images are creating new types of phenotypic data.  Now we have the opportunity to integrate the data at molecular, cellular and tissue scale to create a more comprehensive view of key biological processes underlying complex diseases. Moreover, this integration can have profound contributions toward predicting diagnosis and treatment. The Gevaert lab focuses on achieving progress in multi-scale modeling by tackling challenges in biomedical multi-scale data fusion. Applications are in the area of complex diseases with most projects in the lab focused on oncology, and possible new directions studying neuro-degenerative & cardiovascular diseases.

My group is interested in elucidating the mechanics of cell-matrix interactions in soft tissues. We seek to understand how the mechanical properties of the extracellular matrix regulate processes such as breast cancer progression, stem cell differentiation, and cell division. Further, we aim to determine the biophysics of cell migration and division in confining 3D microenvironments. Our approach involves the use of engineered biomaterials for 3D cell culture and instrumentation to measure forces at the microscale relevant to cells.

Dr. Palesh's research is in the area of cancer control. She is primarily interested in investigating the impact of cancer treatments on sleep, neurocognitive impairment, cancer-related fatigue and quality of life. Her current projects include investigating the impact of behavioral interventions (e.g., behavioral, physical activity, CAM) on improving sleep, circadian function, autonomic nervous system functioning, neurocognitive functioning, fatigue and quality of life in cancer patients and survivors. She is also investigating the relationship between dysregulation of the neuroendocrine stress response system, circadian disruption, sleep problems, fatigue, and disease progression in cancer patients with primary and metastatic cancers. Dr. Palesh's current NIH-funded studies include Phase III RCT of Brief Behavioral Intervention on Sleep, Circadian and ANS function and etiology and long-term outcome of cancer related neurocognitive impairment in newly diagnosed patients with breast cancer. Other projects are focused on understanding cancer survivorship needs and experiences of women diagnozed with cancer.

We are a highly interdisciplinary group with a diverse set of research interests that span various areas of medicine and public health. These interests include i) the use of novel causal inference techniques in electronic health record data to assess the real-life effectiveness of clinical (e.g., medications), behavioral, and health services interventions; ii) deep learning in satellite imagery and other publicly available geotagged data sources to monitor health indicators in low- and middle-income countries; iii) the re-analysis of clinical trial data to gain novel insights; and iv) randomized trials and analysis of household surveys in low- and middle-income countries to improve population health (with a focus on chronic conditions, particularly cardiovascular disease risk factors).

We are a highly interdisciplinary group with a diverse set of research interests that span various areas of medicine and public health. These interests include i) the use of novel causal inference techniques in electronic health record data to assess the real-life effectiveness of clinical (e.g., medications), behavioral, and health services interventions; ii) deep learning in satellite imagery and other publicly available geotagged data sources to monitor health indicators in low- and middle-income countries; iii) the re-analysis of clinical trial data to gain novel insights; and iv) randomized trials and analysis of household surveys in low- and middle-income countries to improve population health (with a focus on chronic conditions, particularly cardiovascular disease risk factors).

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.

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.

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.

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.

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.

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.

The Utz Lab focus is on the normal immune system and how it differs from the immune system of patients with immunodeficiency disorders, infections, and autoimmune diseases. Autoimmune diseases being studied include systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (scleroderma), myositis, primary biliary cirrhosis (PBC), Sjögren's disease, insulin dependent diabetes (type I diabetes or IDDM), multiple sclerosis (MS), inflammatory bowel disease (IBD), and mixed connective tissue disease (MCTD).

Earth’s history is marked by atmospheric and climatic fluctuations that have shaped life and its evolution. Floral and faunal fossils have revealed that these ancient events profoundly changed the abundance and diversity of macroscopic organisms, yet much less is known about how microbial communities responded to these dramatic environmental changes. This is one of the challenges in geomicrobiology - how do we study microorganisms in the context of Earth’s distant past?

While microbes do not readily leave diagnostic morphological fossils, subtle microbial signatures are preserved in sedimentary rocks for billions of years. One such group of biosignatures are well-preserved lipid compounds with specific biological origins, which can be used as biomarkers or "molecular fossils" for the presence of certain microbes or environmental conditions at the time of deposition.

Despite the significant implications biomarker studies have on our interpretation of microbial evolution and Earth’s ancient environment, our understanding of the phylogenetic distribution and physiological function of these molecules in modern bacteria is quite limited. In our lab, we combine techniques from bioinformatics, genetics, physiology and biochemistry to address three general questions that can be applied to any biomarker:

• What is its phylogenetic distribution in modern bacteria?
• What are its physiological roles in modern bacteria?
• What is the evolutionary history of its biosynthetic pathway?

Most of our recent scientific efforts are centered on the role of liver-specific microRNA miR-122 in the hepatitis C virus (HCV) life cycle. Specifically, we discovered that the HCV RNA genome binds two molecules of miR-122 at its 5’ end. This oligomeric complex forms in all HCV genotypes and its main role is to protect the viral RNA from degradation by riboexonucleases. Excitingly, sequestration of miR-122 by modified antisense oligonucleotides results in loss of HCV RNA abundance in cultured cells and infected chimpanzees. Encouraged by these results, Santaris Inc. and Regulus Inc. have performed phase I, and phase II clinical trial in HCV-infected patients. It was found that virus load diminished by several logs in all treated patients. In addition, HCV RNA was non-detectable in a few patients. Thus, treatment of patients with anti-miR-122 oligonucleotides is being explored as an additional option to combat HCV. In addition, we have made the surprising discovery that the HCV genome is fragmented to yield small circular RNAs in infected cells. We are investigating the functional consequences of this finding by hypothesizing that the circular RNAs modulate viral gene expression and innate immune responses in infected and in uninfected bystander cells.

Biomaterials, medical devices, drug delivery, stem cells and 3D bioprinting for musculoskeletal tissue engineering

Biomaterials, medical devices, drug delivery, stem cells and 3D bioprinting for musculoskeletal tissue engineering

Biomaterials, medical devices, drug delivery, stem cells and 3D bioprinting for musculoskeletal tissue engineering

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.

Dr. Yang is a physician-scientist whose research focuses on cardiovascular regeneration and restoration. His laboratory combines stem cell biology with novel imaging technology to advance clinical implementation of induced pluripotent stem cells and their derivatives. Induced pluripotent stem cells and their secretes will trigger a paradigm shift. His research provides a requisite validation with emphasis on clinical translation. Dr. Yang is a Principal Investigator of the National Institute of Health (NIH) funded Cardiovascular Cell Therapy Research Network designed to conduct multi-center clinical trial on novel stem cell therapy. In addition, he leads multiple NIH, foundation, and pharmaceutical research grants along with five clinical trials. He has received several prestigious awards, including the NIH Career Development Award, NIH Career Enhancement Award in Stem Cell Biology, NIH Mid-career Award, and multiple awards from both the American Heart Association and American College of Cardiology. He is a frequent guest speaker and session chair at national and international meetings.

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.

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.

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.

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 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.

The Stanford Urban Informatics Lab & SLAC Grid Integration, Systems, and Mobility (GISMo) group are seeking a post-doctoral fellow to work on the Department of Energy sponsored Impact of Demand Response on short and long term building Energy Efficiency Metrics (IDREEM) project. The goal of this project is to answer the following research questions: Does developing DR capabilities within a building generally lead to more or less efficient buildings (over periods of years)? Does implementing EE strategies within a building generally lead to more or less demand response capacity from those buildings (over periods of years)? Do buildings providing grid services via load shifting consume more energy (over the day) than they would have if not providing services? If so, what are the expected long-term energy impacts? The key outcomes are the establishment of comprehensive long-term DR/efficiency trends; assessment of the system-wide cost, efficiency, and emissions associated with DR; add-ons/extensions to commercial building software models that capture the trends; and a variety of reports, papers, and software documenting our models, methods, and results.

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.

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.