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.

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.

The goals of the Sonnenburg Lab research program are to (i) elucidate the basic mechanisms that underlie dynamics within the gut microbiota and (ii) devise and implement strategies to prevent and treat disease in humans via the gut microbiota. We investigate the principles that govern gut microbial community function and interaction with the host using experimental systems ranging from gnotobiotic mice to humans. We pursue molecular mechanisms of host-microbial interaction using an array of technologies including gnotobiotic and conventional mouse models, quantitative imaging, molecular genetics and synthetic biology, and a metabolomics pipeline focused on defining microbiota-dependent metabolites. The synergy of these diverse techniques provides insight into the dynamics of a microbial ecosystem in response to cues ranging from nutrition to pathogen-induced inflammation. Studies of microbiomes diverse human cohorts, ranging from indigenous populations in Africa, Asia, and South America to dietary intervention trials in cohorts of US residents, have provided great insight into microbiome dynamics and fuel a pipeline of reverse translational studies.

Environmental microbiology (e.g. diatoms, algae) and synthetic biology

Topics: Nitrogen fixation, lipid biosynthesis and transprot, cellular endosymbiosis, nonmodel organisms

Application areas: Fertilizers, Biofuels

At the Feng Lab we are interested in the structure, dynamics and function of eukaryotic transport proteins mediating ions and major nutrients crossing the membrane, the kinetics and regulation of transport processes, the catalytic mechanism of membrane embedded enzymes and the development of small molecule modulators based on the structure and function of membrane proteins.

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.

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 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

Research overview:

How does the cell make and quality control multi-pass membrane proteins like transporters, receptors and ion channels that are essential for cellular physiology? Our lab combines mechanistic cell biology, (structural) biochemistry and protein engineering to dissect the pathways and molecular machines that mature roughly 5,000 human membrane proteins to a fully functional state. We are developing nanobody-based tools to acutely perturb such dynamic intracellular pathways directly at the protein level and assess immediate functional consequences to the nascent (membrane) proteome.

A related area of focus will be to generate highly specific reagents that can fine-tune the cellular stress responses that adjust cellular protein folding and degradation capacity. Such reagents have potential future therapeutic applications as they can be used to either correct or increase the dysregulation of protein homeostasis in neurodegeneration/ageing or cancer, respectively.

Major techniques in the lab include: mammalian cell culture, flow cytometry, FACS, CRISPR knock-outs/ knock-downs/knock-ins, genome-wide perturbation screens, phage & ribosome display, protein purification from mammalian and E. coli cells, in vitro translation and membrane insertion assays. Many of these techniques are highly sought-after in the biotech industry as well.

Tino is the first in his family to attend college (FirstGen) and this experience has shaped his approach to mentorship. The successful candidate will have access to close mentorship and will witness first-hand how to set up a new lab. The lab has fantastic resources and is surrounded by a world-class, collaborative scientific environment. Outside from the lab, life in the sunny Bay area offers spectacular culinary, cultural, and outdoor recreational opportunities. 

The Pleiner lab will be an inclusive space that fosters learning & curiosity, promotes team work and values mentorship to drive an innovative research program that pushes the boundaries of molecular biology. 

Relevant publications:
(*denotes equal contribution co-first- and † denotes co-corresponding authorship)

Stevens, T.A., Tomaleri, G.P., Hazu, M., Wei, S., Nguyen, V.N., DeKalb, C., Voorhees, R.M.† and Pleiner, T.† (2023) A nanobody-based strategy for rapid and scalable purification of native human protein complexes. Nature Protocols

Pleiner, T.*, Hazu, M.*, Pinton Tomaleri, G.*, Nguyen, V.N., Januszyk, K. and Voorhees, R.M. (2023) A selectivity filter in the ER membrane protein complex limits protein misinsertion at the ER. J Cell Biol 222 e202212007. (On the cover)

Pleiner, T., Hazu, M., Tomaleri, G.P., Januszyk, K., Oania, R.S., Sweredoski, M.J., Moradian, A., Guna, A. and Voorhees, R.M. (2021) WNK1 is an assembly factor for the human ER membrane protein complex. Mol Cell, 81, 2693-2704.e12.

Pleiner, T.*, Tomaleri, G.P.*, Januszyk, K.*, Inglis, A.J., Hazu, M. and Voorhees, R.M. (2020) Structural basis for membrane insertion by the human ER membrane protein complex. Science, 369, 433-436.

Pleiner, T.†, Bates, M.† and Görlich, D.† (2018) A toolbox of anti-mouse and anti-rabbit IgG secondary nanobodies. J Cell Biol, 217, 1143-1154.

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).

I'm interested in neuroinflammation and stroke, especially the effects of inflammation on longer term outcomes after stroke. Studies involve mice and humans, and basic mechanistic studies as well as development of potential therapies for humans. Check out the websites above for more information! My lab is welcoming of people from all backgrounds, and promotes team-work and mutual support.

I am also a co-PI on the "Pathways to Neurosciences" program (https://neuroscience.stanford.edu/research/training/pathways-neurosciences), which is not a fellowship but rather a 2-year peer mentoring program to support and provide leadership training to early postdocs and late-stage graduate students who self-identify as coming from groups underrepresented in neuroscience. Please check us out and consider joining after you are on campus!

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.

Our lab is part of the Byers Eye Institute and the Ophthalmology Department at Stanford University. We seek to develop novel retinal imaging technologies to improve the diagnosing and treatment of ocular, vascular, neurodegenerative and systemic diseases. Our work is motivated by the personal interactions with research study volunteers and patients that we have been fortunate to have worked with. We pursue this through a multidisciplinary approach that integrates optics, computer science, vision science, electrical engineering and other engineering disciplines, in a highly collaborative environment with clinical colleagues in our department.

We are studying the molecular mechanisms of neurodegeneration and axon regeneration after CNS injury and neurological diseases, using retinal ganglion cell (RGC) and optic nerve in various optic neuropathies mouse models. Regenerative and neuroprotective therapies have long been sought for CNS neurodegenerative diseases but none have been found. That there is no curative neuroprotective or restorative therapy for neurodegeneration is a central challenge for human health. My lab focuses on the mechanisms responsible for neuronal degeneration and axon regeneration after injury or diseases with the goal of building on this understanding to develop effective combined strategies to promote neuroprotection and functional recovery.

Mission:
Our mission is to understand the role of mechanosensation in the eye and how it relates to glaucoma.

Approach:
Our goal is to discover new strategies for treating glaucoma by understanding the mechanisms of mechanosensation in the eye. By combining human genetic analyses, in vitro molecular and electrophysiological approaches, and in vivo mouse models of glaucoma, we are currently studying the role of mechanosensitive ion channels in glaucoma.

Questions:
· What are the ion channels that mediate pressure sensing in the eye?
· What physiological roles do these channels play in the eye?
· Do these ion channels mediate the development of glaucoma and other ocular pathologies?

Techniques:
· in vitro electrophysiological recording  of ion channel activity
· in vitro optical imaging of ion channel activity
· in vitro mechanical stimulation of individual cells
· genetic manipulation of specific cell types
· mouse models of glaucoma

Our research focuses on unraveling the molecular mechanisms underlying retinal development and diseases. We employ genetic and genomic tools to explore how various retinal cell types, including neurons, glia, and the vasculature, respond to developmental cues and disease insults at the epigenomic and transcriptional levels. In addition, we investigate their interactions and collective contributions to maintain retinal integrity.

Our research interests broadly encompass the molecular mechanisms regulating development, regeneration and repair with a focus on the epigenome. We are exploring epigenetic regulation in health and disease especially understanding (a) the dynamics of DNA methylation and demethylation and (b) the 3D chromatin organization. Another focus is stem cell biology and reprogramming approaches especially utilizing embryonic and induced pluripotent stem cells towards musculoskeletal regeneration and for age-associated diseases like Osteoarthritis. 

We are looking for highly creative and motivated postdoctoral fellows with a broad interest in Stem cell biology and Regenerative medicine. The specific research projects are focused on studying epigenetic regulation of skeletal diseases (cartilage and bone) and for understanding stem cell function in skeletal growth and regeneration. Another focus area is tissue engineering and generation of biomimetic 3D tissue models that reflect the endogenous complexity. Applicants must be PhD (cell, molecular or stem cell biology or bioengineering).

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

We are interested in fundamental aspects of cell-cell recognition, migration and development with the mammalian immune and vascular systems as  models. We use molecular, genetic and single cell transcriptomic and mass cytometric approaches to study  the development and trafficking of  lymphocytes, NK cells and dendritic cells and their role in immune function in health and diseases. 
 
The vascular endothelium controls immune cell recruitment from the blood,  and thus determines the nature and magnitude of immune and inflammatory responses.     In a major new effort, we are applying single cell approaches (scRNAseq and mass cytometry), and novel computational approaches to probe endothelial cell specialization and responses in models of immune and tumor angiogenesis and inflammation.  
 
Although our focus is on fundamental problems in biology, the work is intrinsically translational and the laboratory is interested in applying its  discoveries to models of infection and immune pathology: examples include genetic studies of GPCR's and assessment of novel therapeutics in models of inflammatory bowel disease, psoriasis, cancer, aging and infection.
 
We are actively recruiting fellows with experience in biocomputation and coding who can take advantage of the datasets we are generating;   or experience in vascular biology, immunology,  imaging and cytometry.

One of the key ways that the gut microbiome impacts human health is through the production of bioactive metabolites. By understanding how microbes produce these molecules, we aim to develop new approaches to promote human health and treat disease. Our laboratory employs bacterial genetics, metabolomics, and gnotobiotic mouse colonization to uncover the chemistry that underlies host-microbe interactions in the gut.