Directory - Jane Coffin Childs Memorial Fund

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Karl Herrup, Ph.D. Jane Coffin Childs Fellow

Harvard Medical School

Project Title: Basic mechanisms in the development of the mammalian central nervous system

John W B. Hershey, Ph.D. Jane Coffin Childs Fellow

Cambridge University

Project Title: Organic phosphates

Klemens J. Hertel, Ph.D. Jane Coffin Childs Fellow

Harvard University

Project Title: Splice site selection in alternative splicing

Hans-Martin Herz, Ph.D. Jane Coffin Childs Fellow

Stowers Institute for Medical Research

Project Title: Histone H3K79 methylation in development and cancer pathogenesis

Current research: Identification of the machinery involved in H3K79 methylation and development of small molecular inhibitors against H3K79 methylation.

My interest in biology was awakened during my childhood, mainly through my grandfather who introduced me, through books, to the animal world. Through hobbies like fishing this interest was enforced and carried over into my adolescence. After high school, I started to study classical biology but realized early that I had a more pronounced interest in molecular biology. Starting to make fly food as an undergrad in a lab at the University of Heidelberg in Germany ultimately got me involved in the field of Drosophila genetics and development, and served as the springboard for my decision to move to Houston for my graduate studies. Part of my PhD work was to perform genetic screens to identify cell death regulators in Drosophila. One of the identified candidates turned out also to play a role in the regulation of chromatin. To further expand my experience in biochemical research I joined the lab of Ali Shilatifard in Kansas City. My work here is focused on better understanding the mechanisms by which certain factors regulate transcription through chromatin modification.

Margaret L. Hibbs, Ph.D. Jane Coffin Childs Fellow

Center for Blood Research

Project Title: Characterization of the MAC-1 ligand on neutrophils

Grace N. Hibshman, Ph.D. HHMI-Jane Coffin Childs Fellow

University of California, Berkeley

Project Title: From Bacteria to Biotechnology: Harnessing Retrons for Precision Medicine

CRISPR-Cas systems have revolutionized how specific genes can be precisely edited. Dr. Grace Hibshman’s fellowship project is focused on how to develop the next generation of genome editors.

During her graduate work in Dr. David Taylor’s lab at the University of Texas, Austin, Hibshman became an expert in the structural and functional characterization of CRISPR-Cas systems.

First, she engineered a more specific genome editing tool with less off-target effects. Then, in a tour de force, Hibshman determined the precise 3D structures of this tool in real-time to understand how it recognizes specific sequences of DNA. Her studies have provided crucial insight into how to improve CRISPR-Cas systems for genome editing.

Now, during her postdoctoral research in Dr. Eva Nogales’s lab at UC Berkeley, Hibshman will study a different set of genetic editing tools focusing on retrons, bacterial elements that can fuse multiple enzymatic activities into a single protein. She’ll use biochemical, structural, and high-throughput mutagenesis approaches to characterize and optimize one such retron. Hibshman’s research may provide us with the latest and greatest genome editor, and she’s betting on its applications in a wide variety of diseases such as cystic fibrosis, Alzheimer’s, and Duchenne muscular dystrophy.

Jarvis D. Hill, Ph.D. Jane Coffin Childs Fellow

Yale University

Project Title: Novel Chemical Tools for Targeted Eradication of DNA Repair Proteins and Application to Chemosensitization

Glioblastoma is one of the deadliest forms of brain cancer. All glioblastomas contain fast-growing and aggressive tumor cells. The current standard of care, temozolomide (TMZ), extends patient’s lives by a median of 7 months; however, this chemotherapy only works for a subset of patients, and many of those patients rapidly acquire resistance to this treatment. Additional, more efficacious treatments are direly needed for glioblastoma patients.

Dr. Jarvis Hill’s postdoctoral research in Dr. Seth Herzon’s lab at Yale University aims to enable the next generation of glioblastoma therapies. The Herzon lab recently identified a novel small molecule, KL-50, that is effective against glioblastomas lacking the O6-methylguanine-DNA-methyltransferase (MGMT). However, this small molecule does not work on MGMT-positive glioblastomas. In this research, Dr. Hill will develop tumor-specific MGMT inhibitors that can be combined with KL-50 to treat patients with MGMT-positive glioblastoma.

Part of Dr. Hill’s interest in brain tumors grew out of his Ph.D. research in Dr. David Crich’s lab at the University of Georgia. As an organic chemist, Hill devised a novel synthesis for trisubstituted hydroxylamines. Recognizing that these are underrepresented functional groups in medicinal chemistry, Hill next evaluated the drug-like properties of molecules where he replaced hydrocarbons, ethers, or amines with a trisubstituted hydroxylamine. In contrast with long-standing expectations, Hill found that these substitutions were stable and generally well tolerated. Then, Hill used the trisubstituted hydroxylamine motif as a key structural unit to develop an epidermal growth factor receptor (EGFR) inhibitor with excellent brain penetration, which may be useful for treating brain metastases driven by aberrant EGFR. Now, Dr. Hill will turn his dual focus on synthetic medicinal chemistry and neuro-oncology towards finding glioblastoma therapeutics during his postdoctoral research.

Russell J. Hill, Ph.D. Jane Coffin Childs Fellow

Fred Hutchinson Cancer Center

Project Title: Genetics of C. elegans pharyngeal development

Norbert Bisco B. Hill, Ph.D. Jane Coffin Childs Fellow

University of California, Berkeley

Project Title: Illuminating novel actin cytoskeletal dynamics through a bacterial pathogen

An array of actin modulators promotes actin filament assembly, disassembly, and organization. However, a detailed understanding how this vast network of factors work in concert to precisely regulate actin dynamics is at best incomplete. Many insights into actin regulation have been derived through examining how microbial pathogens manipulate the actin cytoskeleton during infection. The bacterial pathogen Mycobacterium marinum, a close relative of Mycobacterium tuberculosis, has the rare ability to stimulate actin-based motility in the host cytoplasm. However, the bacterial and host factors that contribute to this phenomenon are largely unknown.

Circumstantial evidence suggests M. marinum recruits the actin nucleation promoting factors WASP and N-WASP through an unusual ability to synthesize phosphorylated phosphoinositol (PIP) lipids. Subsequently, M. marinum activates WASP and N-WASP to nucleate actin filaments through an unfamiliar pathway. The goal of this work is to define M. marinum actin-based motility to further illuminate actin regulation at cellular membranes.

Lindsay E. Hinck, Ph.D. Jane Coffin Childs Fellow

University of California, San Francisco

Project Title: Identification of axonal chemotropic receptors

Tom A. Hindmarsh Sten, Ph.D. HHMI-Jane Coffin Childs Fellow

Stanford University

Project Title: Neural Circuit Mechanisms for Balancing Instinct with Experience

Neural circuits have been honed by evolution to enable animals to instinctively survive and reproduce in the world that surrounds them. Mammals, however, also have a distinct ability to weigh primal instinct against experience, allowing us to learn how to appropriately respond based on our unique knowledge of the dynamic world around us. However, how the mammalian brain balances the innate robustness of neural circuits with the flexibility afforded by learning remains unclear.

Dr. Tom Hindmarsh Sten aims to answer these questions as a JCC-HHMI Fellow in Dr. Liqun Luo’s lab at Stanford University. To investigate how instinctive behaviors can be modified by learning, Dr. Hindmarsh Sten will leverage natural variation in the ability of mice to suppress their innate fears and learn how to hunt live prey. He will delineate an anatomical blueprint of neural circuits that mediate evasion and predation, and pinpoint the plastic nodes impacted by learning. These studies will reveal how neural circuits, which have been refined by eons of evolution, are modulated to meet immediate and novel demands in the present.

As a Ph.D. candidate in Dr. Vanessa Ruta’s lab at Rockefeller University, Hindmarsh Sten investigated neural circuits mediating reproduction in fruit flies. He pioneered a novel virtual reality-based behavioral preparation which revealed that sexual arousal in male flies reconfigures how they see and respond to female flies. Additionally, Hindmarsh Sten examined how male flies coordinate aggression amongst rivals with courtship towards females in competitive environments where more than one male fly is vying for each female’s attention. This study revealed neural populations that allow males to rapidly switch between aggression and courtship. With this background, Hindmarsh Sten is primed to investigate how learning modulates innate instinct in mammals.

Victoria L. Hines, Ph.D. Jane Coffin Childs Fellow

University of Basel

Project Title: Function and biogenesis of peroxisome membrane

David C. Hinkle, Ph.D. Jane Coffin Childs Fellow

Harvard Medical School

Project Title: DNA replication in E. coli

Alan G. Hinnebusch, Ph.D. Jane Coffin Childs Fellow

Cornell University /
Massachusetts Institute of Technology

Project Title: Cloning and sequencing of the HIS1 locus in yeast

Carlos B. Hirschberg, Ph.D. Jane Coffin Childs Fellow

Harvard Medical School

Project Title: Metabolism and function of cardiolipin

Rex P. Hjelm, Ph.D. Jane Coffin Childs Fellow

University of Portsmouth

Project Title: Histone I-DNA and histone IV-DN complexes

Tuan-Hua Ho, Ph.D. Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Project Title: Development of D. discoideum

Monto Ho, M.D. Jane Coffin Childs Fellow

Harvard Medical School

Project Title: Mammalian viruses of normal and malignant cells

Theodore T. Ho, Ph.D. HHMI-Jane Coffin Childs Fellow

Stanford University

Project Title: The role of altered neural activity in brain aging and cognitive decline

Both neural activity in different brain regions and behavior change over time and in disease states in both humans and animals, but how exactly activity of single neurons and their associated network dynamics change and directly affect such altered behavior is largely unknown. I am using single-cell optical and electrophysiological neural recording and perturbation techniques to study changes in neural circuit dynamics that control changes in animal behavior.
Previously, I completed a four-year joint bachelor’s/master’s degree program at Harvard University in Human Developmental and Regenerative Biology/Bioengineering, and then I received my PhD in Biophysics from UCSF studying stem cell aging in the lab of Dr. Emmanuelle Passegue.

Frederic L. Hoch, M.D. Jane Coffin Childs Fellow

Massachusetts General Hospital

Project Title: Interrelationships between metals and enzymes

Mark W. Hochstrasser, Ph.D. Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Project Title: Analysis of yeast ubiquitin regulation and function

Ross B. Hodgetts, Ph.D. Jane Coffin Childs Fellow

Yale University

Project Title: Lambda prophage

Alexander Hoffmann, Ph.D. Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Project Title: Host factor regulation of HIV expression

Deborah Hogan, Ph.D. Jane Coffin Childs Fellow

Harvard Medical School

Project Title: Interactions with dual species biofilms

Peter J. Hollenbeck, Ph.D. Jane Coffin Childs Fellow

King's College London

Project Title: A novel microtubule-associated protein causes TP-sensitive aggregation of microtubules

Gunther Hollopeter, Ph.D. HHMI-Jane Coffin Childs Fellow

University of Utah

Project Title: Is PIP2 required for synaptic vesicle exocytosis or endocytosis?

Caroline M. Holmes, Ph.D. Jane Coffin Childs Fellow

Harvard University

Project Title: Learning structure in genotype to phenotype maps

Inferring the genetic basis of quantitative traits is foundational to understanding the biological mechanisms that underlie complex phenotypes such as behavior, homeostasis, and disease. Mapping genotype to phenotype has been transformational for understanding and treating diseases controlled by a single gene, or monogenic. However, understanding complex, highly polygenic phenotypes with currently available approaches can take decades of research from fields of researchers to make progress, if the problem is even solvable with current methodologies.

Dr. Caroline Holmes will transform the process of unraveling polygenic phenotypes in Dr. Michael Desai’s lab at Harvard University. Dr. Holmes will develop new computational approaches and use high-throughput experiments to learn the structure of interactions between genes involved in a particular phenotype. Holmes then will test her predictions of interactions with mutational perturbations. Ultimately, Holmes will develop methods to improve the generalizability of genotype to phenotype maps and test their accuracy on a distinct microbe that was not used to train the system. If successful, Holmes’ methods would rapidly catalyze the process of understanding and rationally perturbing polygenic phenotypes.

Holmes’ longstanding interest in both biology and physics dates back to her studies and research as an undergraduate student at Emory University. Her graduate studies emphasized the physics side as Holmes mainly used theoretical approaches in the labs of Dr. Bialek and Dr. Palmer at Princeton University. However, many of Holmes’ research applications were still biological in nature. For example, Holmes demonstrated that non-24 hour circadian periods can compensate for systematic error that arises as a result of seasonality. Holmes will now develop quantitative experimental systems during her postdoctoral research and combine this with her expertise in theoretical approaches to make inroads into complex polygenic phenotypes.

Leslie J. Holsinger, Ph.D. Jane Coffin Childs Fellow

Stanford University

Project Title: Dissecting converging signaling pathways in T cell activation

Timothy E. Holy, Ph.D. Merck-Jane Coffin Childs Fellow

Harvard University

Project Title: Neural mechanisms of mammalian pheromone recognition

Erik FY. Hom, Ph.D. Jane Coffin Childs Fellow

Harvard University

Project Title: Experimental evolution of symbiosis

Robert W. Honess, Ph.D. Jane Coffin Childs Fellow

University of Chicago

Project Title: Herpes virus specific changes in membrane glycoproteins

Nancy Hopkins, Ph.D. Jane Coffin Childs Fellow

Harvard University /
Cold Spring Harbor Laboratory

Project Title: Life cycle of tumor virus SV40

Image of Sally A. Horne-Badovinac, Ph.D.

Sally A. Horne-Badovinac, Ph.D. Jane Coffin Childs Fellow

University of California, Berkeley

Project Title: Epithelial migration in the drosophila egg chamber

Patricia M. Horvath, Ph.D. HHMI-Jane Coffin Childs Fellow

Harvard University

Project Title: Dissecting the neuronal logic of behavioral hierarchy

Animals rely on instinctive behaviors and homeostatic responses, such as parenting, feeding, mating, and sleeping, to ensure individual and species survival. Maximizing survival requires meeting the most pressing needs at the right time, forcing animals to establish behavioral priorities based on a hierarchy of needs. Neurons controlling many of these behaviors are located within the highly interconnected medial preoptic area of the hypothalamus (MPA), making this structure a likely control hub underlying behavioral hierarchy. However, the neural logic of intra-MPA connectivity and how this directs behavioral priorities across physiological states is unknown.

Using the mouse MPA as a model system, I am studying the cell type-specific structural and functional connectivity underlying key competing behavioral and physiological responses. Further, I am determining how animal states, such as virgin or parent, alter neuron function to induce new behavioral priorities. This work will provide the first depiction of a neural basis of the hierarchy of needs and open new avenues for understanding the neural basis of behavior.

Andrew A. Horwitz, Ph.D. Jane Coffin Childs Fellow

University of California, San Francisco

Project Title: Synthetic chromatin: exploring the design principles of cellular memory

Aaron Hosios, Ph.D. Jane Coffin Childs Fellow

Harvard T.H. Chan School of Public Health

Project Title: Role of the P13K-mTOR signaling network in reprogramming lipid metabolism

To proliferate, cancer cells activate diverse biosynthetic pathways, and determining the critical metabolic pathways will allow new therapies to be developed. Recent studies of cancer metabolism have examined pathways to generate amino acids, nucleotides, and lipids. Studies of lipid metabolism have been largely confined to understanding how cells generate the precursors for de novo lipid synthesis; however, how cells determine the fates of these lipids and how these pathways contribute to proliferation remain undefined. I propose to study the regulation of lipid metabolism downstream of proliferative signaling via the PI3K-mTORC1 network. mTORC1 is a master regulator of cellular metabolism that promotes key anabolic processes, including fatty acid synthesis. My preliminary data suggest that this kinase also regulates the fate of specific lipid pools, favoring synthesis of phospholipids over triglycerides. My proposed studies will define the mechanism and consequences of this regulation. Activating lipid synthesis allows cells to couple membrane expansion to other biosynthetic processes, and I will determine whether the programmed changes in lipid metabolism represent a vulnerability of cells with oncogenic activation of mTORC1. Collectively this study will advance current knowledge of how oncogenic signaling influences cancer metabolism and will define how lipid metabolism contributes to cancer cell proliferation.

Amer A. Hossain, Ph.D. Jane Coffin Childs Fellow

Memorial Sloan Kettering Cancer Center

Project Title: Mechanisms and consequences of APOBEC3 targeting of extrachromosomal DNA

Extrachromosomal DNAs (ecDNAs) are circular DNA elements that amplify oncogenes and mediate chemotherapy resistance. Despite their importance in cancer, currently no therapies directly target these aberrant molecular structures.

Dr. Amer Hossain will investigate innate immune system recognition of ecDNAs to limit their oncogenic potential in Dr. John Maciejowski’s lab at Memorial Sloan Kettering Cancer Center. Dr. Hossain’s research will provide a fundamental understanding of the recognition and processing of ecDNAs by the immune system. Furthermore, his studies may provide insight into defects in this process that lead to cancer, and into therapeutic strategies to reinforce immune clearance of ecDNAs.

Hossain studied bacteria-phage conflicts as a graduate student in Dr. Luciano Marraffini’s lab at The Rockefeller University. Specifically, he developed a novel functional assay to screen for antiphage defense elements, and discovered a DNA glycosylase that inhibits phage replication. At first glance, this might seem like a distant subject from cancer biology. Yet, Hossain notes in many ways the immune-ecDNA conflict mirrors the host-pathogen conflict in that they both involve recognition and degradation of DNA substrates. Therefore, Hossain will apply his expertise to cancer biology during his postdoctoral research.

Hristo Houbaviy, Ph.D. Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Project Title: Biochemical studies of Xist-mediated gene silencing

Fariba Houman, Ph.D. Jane Coffin Childs Fellow

Harvard University

Project Title: Role of CDC14 and a related check point in mitosis

David E. Housman, Ph.D. Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Project Title: DNA synthesis in HeLa cells

Susan C. Howard, Ph.D. Jane Coffin Childs Fellow

Johns Hopkins University

Project Title: Control of ASN-linked oligosaccharide processing

Melissa J. Hoyer, Ph.D. Jane Coffin Childs Fellow

Harvard Medical School

Project Title: Spatial and temporal organelle quality control during changes in cell state

I have always been fascinated by the individual machines of the cell called organelles. In undergrad, I tagged yeast cells with a fluorescent mitochondria reporter. When I looked under the microscope, I was fully hooked. The microscopic world inside the cell was much more elaborate that I could have ever imagined. Subsequently, I decided to continue on to graduate school and study the endoplasmic reticulum (ER) in mammalian cultured cells. The ER is often pictured as this static platform for protein synthesis, but using live cell fluorescence microscopy, you can see how the ER dynamically rearranges its structure: tubules grow out or retract, sheets shrink or expand. This drives a constant remodeling process. For my PhD thesis, I focused on why and how the ER remodels its structure to contact other organelles.

In my current work, I now get to study organelles in neurons. A specialized cell like a neuron maintains a certain shape and structure to properly function. Cells can clear away damaged organelles through the ‚Äúself eating‚Äù process of autophagy. Interestingly, prior evidence indicates that autophagy machinery is needed for human embryonic stem cell differentiation to different cell states. However, to date, there is no established systematic map of organelle-phagy for stem cell conversion to a neuron. Additionally, in human patients with neurodegenerative diseases, including Parkinson‚Äôs disease, many identified gene variants are in autophagy-regulating genes. In my work, I genetically edit and tag stem cells using CRISPR and then convert these cells to neurons. With these engineered induced neurons, I study organelle structure, dynamics, and turnover in order to reveal the underlying mechanisms sustaining the architecture required for healthy and efficient neuronal function.

Christine A. Hrycyna, Ph.D. Jane Coffin Childs Fellow

National Cancer Institute

Project Title: Functional expression and mutational analysis of human P-glycoprotein

Yanyan Hu, Ph.D. HHMI-Jane Coffin Childs Fellow

Dana-Farber Cancer Institute/ Harvard Medical School

Project Title: Unveiling Novel Therapeutic Targets in Cancer Through Cell-Surface Proteomic Profiling

Dr. Yanyan Hu’s research focuses on discovering new biomarkers to help diagnose, monitor, and treat cancer. In particular, Dr. Hu hypothesizes that studying the tumor cell surface proteome will reveal an abundance of potential therapeutic and diagnostic targets against cancer.

In Dr. William Kaelin, Jr.’s lab at Dana-Farber Cancer Institute, Hu has devised a proximity labeling method that enables the direct quantification of proteins on the surface of cancer cells. Hu will now use this method to examine two types of cancer: clear cell renal cell carcinoma, and tumors with homologous recombination defects. In addition to revealing novel and fundamental information on cancer cell surface proteomes, Hu’s research has direct implications for future diagnostic and therapeutic approaches.

Hu’s Ph.D. research in Dr. Sheng Ding’s lab at Tsinghua University focused on totipotent stem cell biology. Totipotent stem cells are capable of producing every kind of differentiated cell in both embryonic and extraembryonic tissues. Previously, they had only been generated through IVF or SCNT using germline cells. Hu discovered a cocktail of three small molecules that converted mouse pluripotent stem cells into totipotent stem cells. Now Hu will apply her expertise of stem cell biology to explore similar mechanisms – such as cellular plasticity, self-renewal, and differentiation – to cancer biology during her postdoctoral research.

Changkun Hu, Ph.D. HHMI-Jane Coffin Childs Fellow

Fred Hutchinson Cancer Center

Project Title: Elucidate the dynamics of kinetochore assembly by singlemolecule imaging

Aneuploidy is a hallmark of cancer development and occurs due to defects in chromosome segregation. The kinetochore, a complex consisting of over 100 different types of proteins, is required for the proper segregation of chromosomes. However, we lack an in depth understanding of the step-by-step assembly process resulting in a functional kinetochore due to the extreme molecular and temporal complexity of this complex. Dr. Changkun Hu will reconstitute kinetochore assembly in vitro and use TIRF microscopy to measure individual kinetochore protein recruitment times in Dr. Sue Biggins’ lab at the Fred Hutch. This approach will allow Dr. Hu to determine rate-limiting steps and key regulating mechanisms in kinetochore assembly and will serve as a blueprint for future studies examining the assembly of other large complexes. Furthermore, this work may reveal novel trouble points in chromosome segregation that lead to aneuploidy in cancer.

As a PhD student in Dr. Nicholas Wallace’s lab at Kansas State University, Dr. Hu’s research focused on the repair of DNA double-strand breaks (DSBs). Dr. Hu demonstrated that beta human papillomavirus type 8 protein E6 (8E6), long known to impair traditional DNA-repair pathways, also promotes DNA repair via a mutagenic DSB repair pathway termed alternative end joining. In this way, 8E6 promotes cancer development by increasing genomic instability. Dr. Hu will now pivot to study genome stability at the chromosome level in Dr. Biggins’ lab.

Jian Hua, Ph.D. Jane Coffin Childs Fellow

Whitehead Institute

Project Title: Analysis of cell expansion regulation in Arabidopsis

Wei Hua, Ph.D. Jane Coffin Childs Fellow

Yale University School of Medicine

Project Title: Mechanism of cell polarity in the sorting pathway

Enoch S. Huang, Ph.D. Jane Coffin Childs Fellow

Washington University in St. Louis

Project Title: Closing the gap: Near-native folds to all-atom models

Wei-Hsiang Huang, Ph.D. HHMI-Jane Coffin Childs Fellow

Stanford University

Project Title: Spatiotemporal dissection of BDNF/TrkB in circuit assembly

Image of Bessie P-H. Huang Gilula, Ph.D.

Bessie P-H. Huang Gilula, Ph.D. Jane Coffin Childs Fellow

Rockefeller University

Project Title: Isolation and characterization of conditions mutations affecting cellular neurotubules

Alex J. Hughes, Ph.D. Merck-Jane Coffin Childs Fellow

University of California, San Francisco

Project Title: Within and between-cell effects of driver mutations on breast tumor fitness

I am applying quantitative engineering approaches to study collective cell phenomena in cancer. Different cells in tumors develop different sets of mutations over time, creating a range of cell clones. One view of the role of cancer mutations is that they enable a small number of progressively malignant clones to take over the tumor one after another. However, mutations can have more complicated effects on tumor progression because their outward effects on the growth of a clone can depend on who their neighbors are. Therefore, I want to understand how cancer mutations affect the overall fitness of tumors by directly measuring it, not just in the cells that contain mutations, but also in neighboring cells. My research aims to shed light on how benign tumors make the transition to proliferative, invasive tumors; perhaps uncovering an Achilles heel to the manipulation of normal cells by mutant ones, leading to new types of cancer therapies.