Directory - Jane Coffin Childs Memorial Fund

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Year Appointed

Institution

Name

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Andrew A. Horwitz Jane Coffin Childs Fellow

University of California, San Francisco

Appointed in 2007

Aaron Hosios Jane Coffin Childs Fellow

Harvard University School of Public Health

Appointed in 2018

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.

Hristo Houbaviy Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Appointed in 2000

Fariba Houman Jane Coffin Childs Fellow

Harvard University

Appointed in 1991

David E. Housman Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Appointed in 1971

Susan C. Howard Jane Coffin Childs Fellow

Johns Hopkins University

Appointed in 1980

Melissa Hoyer Jane Coffin Childs Fellow

Harvard University Medical School

Appointed in 2019

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 Jane Coffin Childs Fellow

National Cancer Institute

Appointed in 1994

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

Fred Hutchinson Cancer Center

Appointed in 2023

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 Jane Coffin Childs Fellow

Whitehead Institute for Biomedical Research

Appointed in 1998

Wei Hua Jane Coffin Childs Fellow

Yale University School of Medicine

Appointed in 2003

Enoch S. Huang Jane Coffin Childs Fellow

Washington University in St. Louis

Appointed in 1997

Wei-Hsiang Huang Jane Coffin Childs - HHMI Fellow

Stanford University

Appointed in 2014

Bessie P-H. Huang Gilula Jane Coffin Childs Fellow

Rockefeller University

Appointed in 1972

Alex Hughes Jane Coffin Childs - Merck Fellow

University of California, San Francisco

Appointed in 2015

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.

Jun R. Huh Jane Coffin Childs Fellow

New York University

Appointed in 2006

David W.L. Hukins Jane Coffin Childs Fellow

Purdue University

Appointed in 1972

Eric H. Humphries Jane Coffin Childs Fellow

Imperial Cancer Research Fund Laboratories, England

Appointed in 1974

Ruei-Jiun Hung Jane Coffin Childs Fellow

Harvard University Medical School

Appointed in 2013

James R. Hunsley Jane Coffin Childs Fellow

Harvard University

Appointed in 1970

John F. Hunt Jane Coffin Childs Fellow

University of Texas Southwestern Medical Center

Appointed in 1992

M. Melissa Hunter-Ensor Jane Coffin Childs Fellow

Massachusetts Institute of Technology

Appointed in 1998

Robert A. Hyman Jane Coffin Childs Fellow

Salk Institute for Biological Studies

Appointed in 1970

Maurizio Iaccarino Jane Coffin Childs Fellow

Stanford University

Appointed in 1966

Kostas Iatrou Jane Coffin Childs Fellow

Harvard University

Appointed in 1978

James A. Imlay Jane Coffin Childs Fellow

Duke University

Appointed in 1987

Jorge A. Iniguez-Lluhi Jane Coffin Childs Fellow

University of California, San Francisco

Appointed in 1994

Sarah Innes-Gold, Ph.D. Jane Coffin Childs - Merck Fellow

Harvard University

Appointed in 2021

Cancer metastasis and immune cell migration require motile movement, meaning the cell membrane must slip relative to the cytoskeleton. Thus, membrane-cytoskeleton attachments in motile cells likely rearrange, allowing tension to propagate across the membrane. In the current literature, there are ~106-fold discrepancies in reported timescales of membrane tension propagation. I hypothesize these discrepancies reflect variability between cell types, arising from differences in membrane microstructure. I specifically hypothesize that in motile cells, transmembrane proteins are arranged to allow membrane flow, enabling rapid tension equilibration, while non-motile cell membranes are structured to impede tension propagation.

I will directly measure tension propagation timescales in motile and non-motile cells and simultaneously characterize the arrangement of cytoskeleton-anchored transmembrane proteins. I will use optical tweezers to stretch membrane tethers, perturbing and measuring tension. I will visualize immobile transmembrane proteins with targeted photochemical labeling and high-resolution fluorescence imaging, revealing how transmembrane protein arrangement regulates membrane fluidity, and how cancer cells might exploit this to metastasize

Arthur A. Iodice Jane Coffin Childs Fellow

University of California, Berkeley

Appointed in 1958

Javier E. Irazoqui Jane Coffin Childs Fellow

Harvard University Medical School

Appointed in 2003

Keith P. Ireton Jane Coffin Childs Fellow

Institut Pasteur, France

Appointed in 1995

Vivian F. Irish Jane Coffin Childs Fellow

University of Cambridge, England /
Yale University

Appointed in 1986

Ralph R. Isberg Jane Coffin Childs Fellow

Stanford University

Appointed in 1983

Shigeki Iwase Jane Coffin Childs Fellow

Harvard University Medical School

Appointed in 2007

Joseph W. Jack Jane Coffin Childs Fellow

Harvard University

Appointed in 1979

Anthony S Jack Jane Coffin Childs Fellow

Harvard University

Appointed in 1972

Allan Jacobson Jane Coffin Childs Fellow

University of Massachusetts Medical School

Appointed in 1975

Deepti Jain Jane Coffin Childs Fellow

Rockefeller University

Appointed in 2003

Aakanksha Jain Jane Coffin Childs Fellow

Boston Children's Hospital

Appointed in 2020

Advancements in vaccine design and immunotherapy have helped us gain insights into how to promote immunity against infections or cancers. However, excessive inflammation associated with immunotherapies, autoimmune diseases, non-healing wounds and even COVID19 is currently at the center of healthcare challenges. Following an inflammatory insult, such as an injury or pathogen invasion, immune cells in the tissues are crucial to resolve inflammation and regain healthy tissue function. Damaging inflammatory signals also activate nearby high threshold sensory neurons‚Äì the nociceptors ‚Äì which are responsible for initiating pain and guarding/withdrawal responses which is believed to prevent further tissue damage. While it is conceivable that nociceptors can cooperate with immune to promote healing, the role of these neurons in shaping the healthy immune landscape of barrier tissues is currently unexplored. In the Woolf lab, I aim to determine the role of nociceptor sensory neurons in restoring the healthy immune profile of barrier tissues following an adverse and painful inflammatory event and develop novel strategies to manipulate neuroimmune interactions using genetic and pharmacological methods. Traditionally, inflammatory conditions are treated with broad immunosuppressants that put the patients at risk for further infections. The ability to fine tune immune function by controlling specific neuronal signals will offer a safer and effective therapeutic strategy for various inflammatory diseases as well as malignancies.

Rishi Jajoo Jane Coffin Childs Fellow

University of California, Los Angeles

Appointed in 2016

The mitochondrion is a subcellular organelle that is the center of energy production, calcium signaling, apoptosis and redox balance for the cell. Therefore, many diseases and normal aging run their molecular course through the mitochondrion. Uniquely, the mitochondrion contains its own DNA and makes RNA and proteins independently from the rest of the cell. This orthogonal system had presented a problem for studying the mitochondrion as the usual genetic tools of the nuclear genome are not available. However, I am using the tools of synthetic biology to allow specific interrogation of mitochondrial protein synthesis in healthy and diseased human cells._x000D_
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In addition to studying mitochondrial protein synthesis, I am developing the yeast mitochondrion as a platform for synthetic biology in order to greatly expand the genetic code and to speed up laboratory evolution. These tools will allow creation of novel therapeutic biopolymers and proteins.

Edward B. Jakobovits Jane Coffin Childs Fellow

University of California, San Francisco

Appointed in 1983

Sirpa T. Jalkanan Jane Coffin Childs Fellow

Stanford University

Appointed in 1984

Philip A. James Jane Coffin Childs Fellow

University of Wisconsin, Madison

Appointed in 1990

John R. James Jane Coffin Childs - HHMI Fellow

University of California, San Francisco

Appointed in 2008

My research involves the reconstruction of the T-cell antigen receptor signaling pathway in an orthogonal cell line to piece apart the molecular details of immune cell triggering, and how the system’s specificity and sensitivity can be genetically encoded.

I am originally from England and did both my undergraduate biochemistry degree and doctoral work at the University of Oxford. Throughout this period, my thoughts became increasingly focused on how signals are transmitted across the impermeable cell membrane, especially where the receptor responsible has no enzymatic activity of its own. For me, this area of research combines cell biology, biochemistry and systems analysis into one very exciting topic which, when applied to cells of the immune system, can have clear implications for new points of therapeutic intervention. Relocating to San Francisco for my postdoc has also provided me with great insights into the similarities and differences between approaches to scientific research on opposite sides of the Atlantic. I hope to combine the best of both worlds when starting my independent career in the near future.

Milan A. Jamrich Jane Coffin Childs Fellow

Yale University

Appointed in 1979

Claudia Janda Jane Coffin Childs Fellow

Stanford University

Appointed in 2010

Working in the lab of K. Christopher Garcia, I am studying the assembly and three-dimensional structures of Wnt-receptor complexes in order to understand Wnt signaling mechanisms, and facilitate development of new strategies to clinically target Wnt-associated diseases.

I have always enjoyed studying biological problems, particularly using structural and biochemical methods to understand underlying molecular mechanisms. ¬†I am most fascinated by fundamental and hard problems that require creativity, tenacity and dedication to solve. ¬†After having studied fundamental aspects of protein translocation, I now wish to examine receptor-ligand interactions with high relevance to human disease. Wnt signaling is important in many developmental and regenerative processes, and in a variety of human diseases, including many types of cancers. However, due to major technical difficulties, there is a complete lack of extracellular structural information about Wnt signaling activation and inhibition. We are using traditional and novel methodologies to obtain structural information that can ultimately facilitate the development of new strategies to therapeutically target Wnt signaling. Most of my spare time is spent running over the hills behind Stanford to train for a marathon, relax from hard work, and think about new ways to approach scientific problems.