Broad Institute Next Generation in Biomedicine Symposium

January 27th, Noon-4:00pm
January 28th, Noon-4:30pm


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2021 Symposium Presenters

Amjad Askary
Amjad Askary, Ph.D.
Postdoctoral Scholar, California Institute of Technology
Synthetic recording of cell lineage and molecular history with image based readout
Multicellular development depends on the individual molecular histories of cells and their descendants, but these histories are usually inaccessible to direct observation. If we could program cells to reveal their clonal relationship, lineage histories, and even their individual molecular trajectories over time, a wide variety of otherwise intractable developmental questions could be answered. In this talk, I present recent technological advances that offer a general solution for mapping cell lineage and molecular transitions while preserving the spatial context of the cells. I will then discuss how this technology can be used to investigate aspects of cell fate specification in the mammalian retina that have remained unclear despite decades of intense study.
Ling Bai, Ph.D.
Jane Coffin Childs Postdoctoral Fellow, University of California, San Francisco
Sensory mechanisms underlying feeding regulation
The gut monitors the quantity and quality of ingested food and provides crucial feedbacks to regulate our feeding behavior, but the sensory systems involved in this process remain poorly defined. Here I will discuss my recent work identifying key sensory cell types in the gastrointestinal tract that control the food intake and food choice.
Robert Banh, Ph.D.
Postdoctoral Fellow, New York University Langone Health
Metabolic Contribution of Neurons, via Peripheral Axons, to Pancreatic Tumorigenesis.
Pancreatic ductal adenocarcinoma (PDAC) tumors have a nutrient poor, desmoplastic, and highly innervated tumor microenvironment. We found that peripheral axons can release serine and glycine (Ser/Gly) to prevent ribosomal stalling on two of the six serine codons during mRNA translation, and to support the growth of exogenous Ser-dependent PDAC cells in Ser-deprived conditions. Moreover, blockade of neuronal innervation decreased PDAC tumor burden in mice on Ser/Gly-free diet, demonstrating that the axonal-cancer metabolic crosstalk supports PDAC growth in nutrient poor environments.
Sofia Beas, Ph.D.
Postdoctoral Research Associate Training (PRAT) Fellow, National Institute of Mental Health
A ventrolateral medulla-midline thalamic circuit for hypoglycemic feeding
Severe glucose deficits trigger organism-wide counter-regulatory responses that aim to restore glucose homeostasis. However, while catecholamine neurons of the ventrolateral medulla (VLMCA) are thought to orchestrate these responses, the circuit and cellular mechanisms underlying specific counter-regulatory responses remained largely unknown. Our work uncovered a previously uncharacterized VLMCA projection to the thalamus that recruits this network to promote feeding behavior during hypoglycemic states.
Zibo Chen, Ph.D.
Damon Runyon Postdoc Fellow, California Institute of Technology
Molecular Programming Using De Novo Designed Proteins
Programmable protein circuits could directly interface with endogenous pathways and provide powerful new functions for the cell, but have been difficult to engineer in a generalizable way. A scalable design for creating specific protein-protein interactions, analogous to base pairing in nucleic acids, would enable this vision. Here, I will describe a scheme to achieve DNA-like modular specificity in proteins based on computationally designed hydrogen bond networks, and show how it allows the creation of mutually orthogonal protein heterodimers, protein-based logic operations, and other programmable protein circuits in mammalian cells.
Yiyin Erin Chen, M.D., Ph.D.
HHMI Hanna Gray Postdoctoral Fellow, Stanford University
Recoding commensal-immune communication for cancer immunotherapy
Immune modulation has become central to treating cancer. Here, we engineer the skin commensal Staphylococcus epidermidis to redirect antigen-specific CD8+ T cells towards cancer cells. Skin colonization with our engineered bacteria reduces tumor burden in vivo in both subcutaneous and metastatic models of melanoma.
Mireia Crispin-Ortuzar
Mireia Crispin-Ortuzar, Ph.D.
Borysiewicz Biomedical Sciences Fellow, Cancer Research UK Cambridge Institute, University of Cambridge
Radiogenomics data integration for predictive oncology
Integrating radiogenomic data for predictive modelling in cancer requires solving the problems of scale and complexity, just as in many other physical systems. In this talk I will talk about how the radiological and cellular scales can be bridged using new co-registration methods. I will also show how the complexity of medical scans can be broken down using computational techniques, and how they can be integrated into multi-omics models to predict treatment response.
Kacie D Deters
Kacie D Deters, Ph.D.
Postdoctoral Fellow, Stanford University
Risk factors for aging and Alzheimer’s disease in Blacks
Alzheimer’s disease is overrepresented in the U.S. Black population by almost 2 fold, which may be due to racial disparities in certain risk factors (eg. vascular, social, genetic, etc.). We determined if a priori genetic risk factors might impact cognitive decline and neuropathology as a function of genetic ancestry and/or self-identification in Black and White individuals. This research can provide valuable information in identifying the underlying cause to some of the disparities that exist between Blacks and Whites and have the potential to enhance individual risk estimates for disease status.
Melinda Diver, Ph.D.
NCCIH K99/R00 Pathway to Independence Awardee; Postdoctoral Fellow,
University of California, San Francisco
Structural insights into the analgesic drug target TRPM8
The sensation of pain protects our bodies from harm, but maladaptive changes in this sensory modality can lead to debilitating persistent pain disorders. To enhance our molecular understanding of pain sensation, I have determined cryo-EM structures of the cold and menthol receptor TRPM8 in distinct conformational states, including its ligand-free form and those in complex with antagonists or calcium. This work provides a mechanistic rationale for known biological properties of TRPM8 and promises to facilitate the design of drugs that modulate aberrant channel activity under pathophysiological conditions.
Ariangela Kozik
Ariangela J Kozik, Ph.D.
Research Fellow, Yvonne Huang Lab, University of Michigan
The Airway Microbiome and Inflammation in Asthma Phenotype
The respiratory microbiome has been identified as a potentially prominent influence in airway immune homeostasis. However, our knowledge of the specific role of the airway microbiome in adult asthma is limited. Understanding the microbial-immune relationships that contribute to asthma pathogenesis and presentation will inform more precise diagnostic and therapeutic strategies.
James Nunez
James Nuñez, Ph.D.
HHMI Hanna Gray Fellow, University of California, San Francisco
Programmable transcriptional memory by CRISPR-based epigenome editing
A general approach for heritably altering gene expression would enable many discovery and therapeutic efforts. I will present the advent of the CRISPRoff technology - a programmable single protein that heritably silences gene expression by introducing DNA methylation and repressive histone genes. CRISPRoff enables diverse applications such as genome-wide screens, multiplexed cell engineering, and mechanistic exploration of epigenetic inheritance.
Florentine Rutaganira
Florentine Rutaganira, Ph.D.
HHMI Hanna Gray Postdoctoral Fellow, UC Berkeley Department of Molecular and Cellular Biology
Chemical Genetic Assessment of Tyrosine Kinase Signaling in the Animal Stem Lineage
Choanoflagellates, the closest living relatives of animals, possess a full tyrosine kinase signaling repertoire that was previously thought to be restricted to animals. Using kinase-directed pharmacology and high-content imaging in the choanoflagellate Salpingoeca rosetta, I have identified compounds that affect S. rosetta proliferation and colony formation. Findings from this study suggest that tyrosine kinase function evolved before the origin of animals.
Chelsey Spriggs, Ph.D.
Burroughs Wellcome Fund PDEP Fellow; Postdoctoral Fellow, University of Michigan
Hijacking host motor proteins for viral entry
During entry, most DNA viruses must navigate the crowded cellular environment to reach the nucleus where transcription and replication of the viral genome occur. How polyomavirus (PyV), a small, DNA tumor virus, accomplishes this essential step in infection is unclear. Here, I will describe an unexpected and novel role for host motor proteins in this process and the next big questions in the field.
Tyler Starr
Tyler Starr, Ph.D.
HHMI Damon Runyon Postdoc, Fred Hutchinson Cancer Research Center
Functional and antigenic evolution of the SARS-CoV-2 receptor-binding domain
The receptor-binding domain of the SARS-CoV-2 spike mediates binding to ACE2 receptor, and is a major determinant of host range and a dominant target of neutralizing antibodies. We have applied deep mutational scanning approaches to characterize the functional and antigenic evolution of the SARS-CoV-2 and related coronavirus receptor-binding domains.
Mathew Stracey
Mathew Stracey, Ph.D.
Sir Henry Wellcome Postdoctoral Fellow, University of Oxford
Developing personalized treatment strategies which minimize the emergence of antibiotic resistance.
Antibiotics are a double-edged sword: they help cure the current infection, but they also select for resistant pathogens, making future infections harder to treat. This is particularly problematic in urinary tract infections (UTIs), which frequently recur. Using machine-learning analysis of clinical records from 200,000 patients together with whole genome sequencing of 1200 urine culture isolates we show that the risk that a patient gains a resistant UTI following antibiotic treatment can be reduced by 48% using personalized antibiotic recommendations. This tailored treatment approach based on the patient's infection history offers a promising route to improving both individual outcomes and minimizing the spread of resistant pathogens.
Jhimmy Talbot, Ph.D.
Postdoctoral fellow, New York University School of Medicine
Neuroimmune circuits regulate intestinal immune-metabolic homeostasis
I identified a feeding- and circadian-regulated interaction between neurons and immune cells that promotes a trade-off between innate immune protection and the efficiency of nutrient absorption.
Tong Wu
Tong Wu, Ph.D.
Postdoctoral fellow, University of Chicago
Kethoxal-assisted profiling of transcription dynamics and RNA-RNA interactions
We designed a N3-kethoxal molecule that specifically labels and enriches single-stranded DNA (ssDNA) and single-stranded RNA (ssRNA). N3-kethoxal-assisted ssDNA sequencing (KAS-seq) profiles transcription dynamics and non-B form DNA structures in a 5-minute time scale, by using mouse tissues or as few as 1,000 cells. Conjugated with multifunctional crosslinkers, N3-kethoxal also facilitates the detection of RNA-RNA interactions in the context of mRNP complexes.
Kathryn Yost
Kathryn Yost, Ph.D. Candidate
NCI F99 Predoctoral Fellow, Stanford University
EcDNA hubs drive cooperative intermolecular oncogene expression
Extrachromosomal DNAs (ecDNAs) are prevalent in human cancers and mediate high oncogene expression through elevated copy number and altered gene regulation. We find that ecDNA hubs, comprised of ~10-100 ecDNAs clustered in the nucleus of interphase cells, drive intermolecular enhancer input for amplified oncogene expression. These results nominate ecDNA hubs, rather than individual ecDNAs, as units of oncogene function, cooperative evolution, and new targets for cancer therapy.
Ziyang Zhang
Ziyang Zhang, Ph.D.
Damon Runyon Cancer Research Foundation Postdoctoral Fellow, University of California, San Francisco
A Chemical Strategy for Brain-specific Inhibition of mTOR
On-target-off-tissue drug engagement is an important source of adverse effects that constrains the therapeutic window of drug candidates. In central nervous system diseases, drugs with brain-restricted pharmacology are highly desirable. In this talk I will introduce a chemical trick to achieve “brain-only” inhibition of the protein kinase mTOR and show its application in the treatment of glioblastoma as well as alcohol use disorder.
Xin Zhou
Xin Zhou, Ph.D.
Damon Runyon Postdoctoral Research Fellow, University of California, San Francisco
Engineering biological functions with synthetic protein switches
Synthetic protein switches, which detect a user-defined signal and convert it to a specific response, are invaluable tools in research and medicine. In my past research, I’ve studied and engineered 4 different protein switches, including light-responsive proteins, phosphotyrosine binders, protein arginine deiminase 4 conformation switches, and most recently, biosensors to detect SARS-CoV-2 antibodies. In this presentation I will introduce the engineering of a couple of these synthetic protein switches and the exciting applications in both fundamental research and translational diagnostics and medicine.