PRISM Mentors

A major aim of our lab is to define metrics of immune competence in various settings, including cancer immunotherapy, organ transplantation, allergy, and chronic viral infection.  We use CyTOF mass cytometry, often in combination with other technologies, to broadly survey immune features at the cellular level, then examine links between features or groups of features and clinical outcome.  A long-term goal is to create an assay of global immune competence that could predict risk for various immune-related outcomes in both healthy individuals and in disease.

We study how the interactions between enteric bacterial pathogens, the gut microbiota and the immune system influence chronic infection and transmission to new hosts. Salmonella is one of the model pathogens that we study. Salmonella typhi cause systemic diseases such as typhoid fever. we also explore interactions between Salmonella and immune cells, such as macrophages. We have shown that persisting Salmonella exploit the metabolic immune state of alternatively activated macrophages in order to cause chronic infections.

We are very interested in human-adapted Salmonella and are trying to understand the evolution of the strains of Salmonella that cause typhoid fever. Recently we have developed a tool to study the genomes of various Salmonella and how the genes contribute to surviving the various stresses that the pathogens encounter during infection, including human macrophages.

My group is intersted in preventing sickness following infections.  We do this not by limiting microbe load, but by increasing the body's tolerance and resilience to damage.  In the past we worked mostly on fruitflies, but have switched to studying mice and humans and focusing on malaria.  We try to identify modifiable physiological systems that we can perturb to improve health outcomes.  

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 seeks to decipher the genetic, molecular and physical basis of touch sensation and its disruption by mechanical and chemical stress, such as exposure to elevated glucose in diabetes and chemotherapeutic drugs. We use a combination of genetics, electrophysiology, and quantitative analysis of behavior and also develop new tools for delivering and measuring mechanical force.  We also lead an interdisciplinary project (NeuroPlant) that uses nematode behavior to identify compounds synthesized by medicinal plants that modulate neuron function.  This project also seeks to link compounds to their conserved protein receptors.

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.

Our laboratory studies the mechanisms by which highly complex behaviors are mediated at the neuronal level, mainly focusing on the example of dynamic social interactions and the neural circuits that drive them. From dyadic interactions to group dynamics and collective decision making, the lab seeks a mechanistic understanding for the fundamental building blocks of societies, such as cooperation, empathy, fairness and reciprocity. The computations underlying social interactions are highly distributed across many brain areas. Our lab is interested in which specific areas are involved in a particular function, why such an architecture arises and how activity in multiple networks is coordinated. Our goal is to develop a roadmap of the social brain and use it for guiding restorative treatments for conditions in which social behavior is impaired, such as Autism Spectrum Disorders and Schizophrenia.

The goal of our research is to understand the algorithms the brain uses to learn. A fundamental feature of our neural circuits is their plasticity, or ability to change. How does the brain use this plasticity to tune its own performance? What are the learning rules that determine whether a neural circuit changes in response to a given experience, and which specific neurons or synapses are altered?  Our research integrates molecular, cellular, systems and computational neuroscience approaches in mice to uncover the logic of how the cerebellum implements learning.

How do cells in our nervous system develop highly specialized functions after birth, and how do they degenerate as we age? An emerging molecular mechanism is 3D genome architecture—the folding of 6 billion base pairs of DNA (~2 meters) into a tiny cell nucleus (~10 microns). This folding can strategically position genes and their regulatory elements in 3D to orchestrate dynamic gene expression, and has been implicated in many developmental and degenerative diseases (e.g., autism, schizophrenia, Alzheimer’s). However, traditional technologies and algorithms struggle to capture the full complexity of genome architecture of a single cell, and the enormous heterogeneity between cells. In addition, most studies interrogate genome architecture in vitro, taking cells out of their physiological context. The Tan Laboratory of 3D Genomics at Stanford Neurobiology studies the single-cell 3D genome architectural basis of neurodevelopment and aging by developing the next generation of in vivo multi-omic assays and algorithms, and applying them to the human and mouse cerebellum and beyond (e.g., cancer, immunology).

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.

Epilepsy affects ~1% of all children and is defined by recurrent, unprovoked seizures, impaired cognitive abilities, and diminished quality of life. The predisposition for seizures is thought to result from abnormal plasticity and excessive synchrony in affected neural networks. Myelin plasticity is a newly recognized mode of activity-dependent neural network adaptation. The potential for dysregulated myelin plasticity in disease states such as epilepsy is unexplored. Myelination of axons increases conduction velocity and promotes coordinated network function including oscillatory synchrony. During and after age-dependent developmental myelination, increases in myelin occur when humans and rodents acquire new skills. While adaptive myelin plasticity modulates networks to support function in the healthy state, it is unknown whether this process also contributes to network dysfunction in neurological disease.

The Knowles lab conducts basic, translational and clinical research to study how seizures shape white matter, and how changes in white matter shape the course of epilepsy and its comorbidities. We discovered that generalized (absence) seizures induce aberrant myelination that promotes seizure progression. Thus, maladaptive myelination may be a novel pathogenic mechanism in epilepsy and other neurological diseases.  Using innovative imaging, electrophysiological, histological and molecular biology techniques, we are studying multiple questions.

How does white matter structure change throughout the brain over the course of epilepsy? How does white matter structure impact network synchronization, seizures and cognition? What signaling pathways underlie aberrant white matter plasticity in different forms of epilepsy? What can we learn from white matter changes found with various imaging modalities in humans with epilepsy?

Our research aims to fill a fundamental gap of knowledge about the timing, location, and causal importance of specific neuronal populations in the brain that work together in the millisecond scale to subserve a given brain function.

We record directly from inside the brain in neurosurgical patients that are implanted with multiple electrodes across different anatomical and functional systems. We also apply direct electrical current to specific populations of neurons to alter their function while testing the effect of such perturbation on the human participant subjective feelings or task performance.

Our research is beneficial to each individual patient who volunteers to participate in our cognitive and behavioral experiments because we map the location of functional units within each patient’s brain and share this information with clinicians to make more precise and safer surgical plans and prevent major cognitive deficits after surgery.  We also map the location of pathological activity  and use the data to locate the source of seizures and the pathways for their propagation in each individual patient’s brain.

Our work is also relevant to public health and has societal impact. We strive to collect novel information about the functional architecture of the human brain, and improve our understanding of how the brain works. This will be vital for our understanding of the pathophysiology of neurological and psychiatric disorders that affect higher level cognitive functions and cause major problems for afflicted individuals and their families and the society.

We study human brain function at multiple levels of cognitive and behavioral processing. We study brain activity from the very early sensory input to very late decision making in even social or emotional domains. We do not focus on a specific area of the brain or on a narrow field of cognitive neuroscience. As documented by our published work, every level of human cognition, every stage of human brain function, and every regions of the human brain - are of interest to us – as we want to understand how different areas of the brain work together across different experimental tasks. For instance, we have studied the prefrontal cortex (PFC) as we have recorded directly from the human periaqueductal gray (PAG) and we have electrically stimulated the human default network as we have stimulated the human hypothalamus.  Our goal is to acquire a universal understanding of the functional architecture of the human brain with millisecond and millimeter precision.

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

Our research focuses on genetic forms of hearing loss and vestibular dysfunction. As many features of the auditory/vestibular system are highly conserved among vertebrates, we use zebrafish as our animal model and have identified over a dozen genes that are required for hearing and balance. Our studies have yielded important insights into the molecular basis of sensory hair-cell function, especially with regard to mechanotransduction and synaptic transmission. To understand the function of deafness genes and delve deeper into the underlying biology, our lab uses a wide range of methods to analyze mutant phenotypes including live cell imaging, physiological experiments, CRISPR gene editing, transcriptomic methods, and auditory/vestibular behavioral analyses. Department URL: https://med.stanford.edu/ohns.html

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.