PRISM Mentors

The Yeh Lab studies the apicoplast, a unique plastid organelle in Plasmodium falciparum parasites that cause malaria. We are particularly focused on unbiased chemical and genetic screens to discover new cell biology and therapeutic targets for this important global health disease. Our work highlights the untapped opportunities in exploring divergent biology in non-model organisms, a theme we plan to expand in the lab by studying ocean algae (malaria's cousins!) and their role in the global ecosystem.

The @wormsenseLab at Stanford University seeks postdoctoral scholars with an interest in the genetics, biophysics, and cell biology of sensation. Experience with in vivo and in vitro live imaging as well as gene-editing techniques in a genetic model organism such as C. elegans is preferred, but not essential. In appointing postdocs, we look for curiosity, excellence in the practice of reproducible research, and the ability to lead and work in teams — learning from and teaching others. You may launch research into the molecular and physical events responsible for touch and its degradation by persistent mechanical stress and chemotherapeutics. The latter project involves a collaboration with Katie Wilkinson (Prof. Biology, SJSU), an expert in rodent proprioception. You may also propose to join NeuroPlant, an interdisciplinary, team-based discovery platform for discovering novel ligand-receptor pairs that modulate nervous system function and for deciphering the neural codes responsible for chemical attraction and repulsion. As a NeuroPlant postdoc, you will be encouraged to select a co-advisor from the project faculty team. The @wormsenseLab believes that interdisciplinary scientists are needed in diverse careers and have helped to launch former postdocs into tenure-track academic positions, research and business development in industry, start-ups, and venture capital firms.

The @wormsenseLab at Stanford University seeks postdoctoral scholars with an interest in the genetics, biophysics, and cell biology of sensation.  In appointing postdocs, we look for curiosity, excellence in the practice of reproducible research, and the ability to lead and work in teams — learning from and teaching others. You may launch research into the molecular and physical events responsible for touch and its degradation by persistent mechanical stress and chemotherapeutics.  You may also propose to join NeuroPlant, an interdisciplinary, team-based discovery platform for discovering novel ligand-receptor pairs that modulate nervous system function and for deciphering the neural codes responsible for chemical attraction and repulsion. As a NeuroPlant postdoc, you will be encouraged to select a co-advisor from the project faculty team. The @wormsenseLab believes that interdisciplinary scientists are needed in diverse careers and have helped to launch former postdocs into tenure-track academic positions, research and business development in industry, start-ups, and venture capital firms. You can learn more about our researchers from this 2019 Life in a Lab profile.

The Maduke laboratory at Stanford University is seeking a postdoctoral scholar to study the molecular mechanisms of chloride-selective channels and transporters. Chloride channels and transporters are expressed ubiquitously, with defects giving rise to human diseases of kidney and bone, disorders of blood-pressure regulation, and epilepsy.  Projects in the lab seek to understand the molecular basis for these functions using a combination of electrophysiology, biochemistry, and a variety of structural and spectroscopic techniques, tightly integrated with results from computational collaborations. Experience in electrophysiology, structural biology, or membrane protein biochemistry is helpful but is not necessary.  More important is a strong personal motivation and willingness to learn.



Relevant publications include:



• Khantwal, C.M., et al. (2016) Revealing an outward-facing open conformational state in a CLC Cl-/H+ exchange transporter. Elife Jan 22;5. pii: e11189. doi: 10.7554/eLife.11189.


• Abraham, S.J., Cheng, R.C., Chew, T.A., Khantwal, C.M., Liu, C.W., Gong, S. Nakamoto, R.K., and Maduke, M. (2015). 13C NMR detects conformational change in the 100-kD membrane transporter ClC-ec1. J Biomol NMR, 61(3-4), 209-26.


• Han, W., Cheng, R.C., Maduke, M.* and Tajkhorshid, E.* (2014). Water Access Points and Hydration Pathways in ClC H+/Cl− Transporters. PNAS, 111: 1819–1824. PMCID: PMC3918786

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.

My research program uses the fruit fly Drosophila to investigate neural circuits at the cellular and molecular levels. In this context, we predominantly study circuits involved in visual processing, particularly motion detection, as well as the sensorimotor transformations that underpin visually-guided locomotion. The development of novel molecular techniques is crucial for this work. Our ongoing research encompasses three types of tools: high-speed voltage imaging using genetically encoded indicators (like those you propose to optimize) using a variety of imaging strategies, cell-type-specific gene disruption tools, and molecular perturbations of energy metabolism in the brain. In addition, we are very interested in how the molecular underpinnings of neurodegenerative diseases like Parkinson's Disease alter neuronal function, and use the fly as a model system in which to better dissect these disorders.

Our specific main goals are to:

1. Discover strategies for halting and reversing vision loss in blinding diseases.

2. Understand how visual perceptions and arousal states are integrated to impact behavioral responses.

We use a large range of state-of-the-art tools: virtual reality, gene therapy, anatomy, electrophysiology and imaging and behavioral analyses.

Nirao Shah's lab is interested in understanding the molecular and neural networks that regulate sexually dimorphic social behaviors.

My work focuses on neuroimmunology and how the central and peripheral immune system responds to brain injury, and in particular, stroke. We study how microglia and astrocytes respond with an emphasis on both the basic biology and clinically-relevant outcomes. We are also interested in how stroke can provoke long-lasting adaptive immune responses that lead to post-stroke dementia, a serious and currently untreatable consequence of stroke. The basic science lab performs primarily studies in mice and on human samples, while the Stanford Stroke Recovery Program (https://med.stanford.edu/neurology/divisions/stroke/recovery.html) enrolls stroke survivors and collects clinical data and human samples to ask whether findings in mice are applicable to humans. My lab values diversity of all types and there are projects available for postdoctoral scholars either in mouse or human studies.

I direct the NIH supported T32 Epilepsy postdoctoral training program, with faculty broadly interested in the cellular/circuit basis of normal brain excitability and how it is disrupted in the disease of epilepsy.  My particular interest is in large scale brain rhythms occuring during childhood absence epilepsy as studied in animal models.

Alzheimer's disease pathology begins decades before clinical symptoms of dementia are present, providing an important opportunity to understand early disease and the impact of this disease on cognitive aging.  We combine multimodal neuroimaging and genetics to determine how AD changes and risk factors influence subtle cognitive decline in older individuals. We have a particular focus on PET imaging of Amyloid and Tau proteins, but also work with structural and functional MRI data. The ultimate goals of our work are to improve our ability to predict who is most at risk for dementia, and to understand the time course of brain changes that occur decades before clinical symptoms are present.  We are specifically recruiting trainees with expertise in genetics, neuroimaging, or neuropsychology, to work on large scale multimodal imaging-genetic studies.

The Poston Lab seeks to understand the biological underpinnings of non-motor symptoms in patients with Lewy Body diseases, such as Parkinson's disease and Lewy Body Dementia. While our primary focus is understanding cognition and dementia, we also study other prominent non-motor symptoms such as psychosis/hallucinations, sleep disruption, orthostatic dysregulation, and others.  A major focus is on the role of co-pathologies, such as Alzheimer's and vascular co-pathologies, and the role of neuro-inflammation, in the development of Lewy Body disease associated non-motor symptoms.  We collect clinical, motor, neuropsychological, biological, genetic, and imaging data on patients and healthy older adults to perform our studies. 

We work on the cellular and molecular basis of neuronal survival and axon growth relevant to neuroprotection and regeneration, and on differentiation and transplant relevant to neural development and cell replacement therapies. Using retinal ganglion cells, a type of CNS neuron, as our primary model system in vitro and in rodent models in vivo, we use diverse "omics" and discovery research, combined with hypothesis-driven experiments and novel techniques, to unveil the basis for neuronal development, integration, and regeneration in the visual system.

Specificity and efficacy in intracellular signal transduction can be conferred by the anchoring and co-localization of key enzymes and their upstream activators and substrate effectors by scaffold proteins. The Kapiloff lab investigates “signalosomes” formed by scaffold proteins, asking fundamental questions such as: 1) how are signalosomes constituted; 2) how are upstream signals integrated by signalosomes to regulate in a concerted manner downstream effectors; 3) what is the physiologic relevance of these signalosomes; and 4) can signalosomes be targeted in a clinically relevant manner so as to constitute new therapeutic strategies. In particular, the Kapiloff lab studies signaling within the myocardium and retina. Using a comprehensive approach that includes biochemistry, cell biology, and in vivo physiology, ongoing projects address the regulation of pathological cardiac remodeling and the effects of disease on retinal neurons.

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 translational research laboratory endeavors to bring breakthroughs in stem cell biology and tissue engineering to clinical ophthalmology and reconstructive surgery. Over 6 million people worldwide are afflicted with corneal blindness, usually caused by chemical and thermal burns, ocular cicatricial pemphigoid, Stevens-Johnson syndrome, microbial infections, or chronic inflammation. These injuries often result in corneal vascularization, conjunctivalization, scarring, and opacification from limbal epithelial stem cell (LSC) deficiency (LSCD), for which there is currently no durable treatment.

The most promising cure for bilateral LSCD is finding an autologous source of limbal epithelial cells for transplantation. Utilizing recent advances in the field of induced pluripotent stem cells (iPSC), our research aims to create a reliable and renewable source of limbal epithelial cells for potential use in treating human eye diseases. These cells will be grown on resorbable biomatrices to generate stable transplantable corneal tissue. These studies will serve as the basis for human clinical trials and make regenerative medicine a reality for those with sight-threatening disease. On a broader level, this experimental approach could serve as a paradigm for the creation of other transplantable tissue for use throughout the body. Stem cell biology has the potential to influence every field of medicine and will revolutionize the way we perform surgery.

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

I am a surgeon-scientist with a clinical interest in caring for patients with hearing loss and deafness, and research interests in inner ear development and regeneration. For almost 20 years, I have been studying hair cell biology. Since 2007, my research has focused on defining the role of Wnt signaling in regulating hair cell progenitors in the developing and damaged inner ear using a combination of genetic, molecular biological, pharmacological, and imaging techniques. In particular, our work has led to the discovery of Wnt-responsive hair cell progenitors in the neonatal mouse cochlea and utricle, and more recently, functional recovery during vestibular regeneration.

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

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.

Dr. Cong's group is developing novel technology for genome editing and single-cell genomics, leveraging scalable methods inspired by data science and machine learning and artificial intelligence.

His group has a focus on using these gene-editing tools to study immunological and neurological diseases. His work has led to one of the first FDA-approved clinical trials using CRISPR/Cas9 gene-editing for in vivo gene therapy. More recently, his group invented tools for cleavage-free large gene insertion via mining microbial recombination protein (Wang et al. 2022), and developed single-cell perturbating - tracking approach for studying cancer immunology and neuro-immunology (Hughes et al. 2022). We have also strong interest in using deep learning for predicting and designing gene-editing system and protein function (Hughes et al. 2022 and Yuan et al. 2023). Dr. Cong is a recipient of the NIH/NHGRI Genomic Innovator Award, a Baxter Foundation Faculty Scholar, and has been selected by Clarivate Web of Science as a Highly Cited Researcher.

Our lab studies the mechanisms by which cells and organisms respond to genetic change. The genetic landscape faced by a living cell is constantly changing. Developmental transitions, environmental shifts, and pathogenic invasions lend a dynamic character to both the genome and its activity pattern.We study a variety of natural mechanisms that are utilized by cells adapting to genetic change. These include mechanisms activated during normal development and systems for detecting and responding to foreign or unwanted genetic activity. At the root of these studies are questions of how a cell can distinguish "self" versus "nonself" and "wanted" versus "unwanted" gene expression. We primarily make use of the nematode C. elegans in our experimental studies. C. elegans is small, easily cultured, and can readily be made to accept foreign DNA or RNA. The results of such experiments have outlined a number of concerted responses that recognize (and in most cases work to silence) the foreign nucleic acid. One such mechanism ("RNAi") responds to double stranded character in RNA: either as introduced experimentally into the organism or as produced from foreign DNA that has not undergone selection to avoid a dsRNA response. Much of the current effort in the lab is directed toward a molecular understanding of the RNAi machinery and its roles in the cell. RNAi is not the only cellular defense against unwanted nucleic acid, and substantial current effort in the lab is also directed at identification of other triggers and mechanisms used in recognition and response to foreign information.

Energy metabolism encompasses the fundamental homeostatic processes by which we regulate our energy storage and energy expenditure. Energy metabolism is highly dynamic and changes according to availability of nutrients, physical activity, or environmental conditions. Dysregulation of energy metabolism is a hallmark of many age-associated chronic diseases, including obesity, type 2 diabetes, dyslipidemias, neurodegeneration, and cancer. Therefore a complete understanding of the molecular pathways of energy metabolism represents an important basic scientific goal with implications for many of the most pressing biomedical problems of our generation. Metabolic tissues including adipose, liver, and muscle play critical roles in energy homeostasis. We are interested in understanding the dynamic endocrine signals that control metabolic tissue function. What are the identities of these signals? How do their levels change in response to physiologic energy stressors? Where are they made? What cell types or tissues do they act on? To answer these questions, we use chemical and mass spectrometry-based technologies as discovery tools. We combine these tools with classical biochemical and genetic techniques in cellular and animal models. Our goal is to discover new molecules and signaling pathways that regulate organismal energy metabolism. Recent studies from our laboratory have identified a family of cold-regulated lipid hormones that stimulate mitochondrial respiration as well as a thermogenic polypeptide hormone regulated by exercise. We suspect that many more remain to be discovered. We anticipate that our approach will uncover fundamental homeostatic mechanisms that control mammalian energy metabolism. In the long term, we hope to translate our discoveries into therapeutic opportunities that matter for metabolic and other age-associated chronic diseases.

Mitochondrial dysfunction is commonly associated with aging and age-related chronic diseases. A major goal of our research is to understand how mitochondrial dysfunction arises during aging and contributes to the pathogenesis of a broad spectrum of age-related diseases, from cancer to neurodegenerative diseases and sarcopenia. An overarching hypothesis is that aging and age-related diseases share  fundamental molecular and cellular mechanisms. Thus, by targeting the molecular drivers of aging, we can develop new understandings and therapies for many age-related diseases. Supporting this hypothesis, our more recent studies demonstrate that reverse electron transport (RET) along mitochondrial electron transport chain is activated during aging, leading to excessive reactive oxygen species (ROS) production and imbalanced NAD+/NADH ratio, and that inhibition of RET is beneficial in disease models of brain tumors and neurodegenerative diseases. We are actively investigating the mechanism of RET activation during aging, the signaling pathways influenced by RET, and the potential of RET as a viable therapeutic target. We use Drosophila and mouse in vivo models, human induced pluropotent stem cell (iPSC) derived cell culture models, and state-of-the art techniques such as CRISPRa/i, proximity proteomics, RNA-seq, cryo-EM, and molecular dynamics simulation in our research.

Research in the Pollack lab centers on translational genomics, with a current focus on diseases of the prostate. The lab employs next-generation sequencing, single-cell genomics, genome editing, and cell/tissue-based modeling to uncover disease mechanisms, biomarkers and therapeutic targets. Current areas of emphasis include: (1) Defining molecular features of prostate cancer that distinguish indolent from aggressive disease; (2) Determining disease mechanisms and new therapeutic targets in benign prostatic hyperplasia (BPH); and (3) Defining disease drivers in rare neoplasms (e.g., ameloblastoma).