The Charles A. King Trust Fellowship Program Funds 21 Early Career Scientists Investigating the Causes and Treatment of Human Disease

The Charles A. King Trust Fellowship Program has announced the selection of the 2022 cohort of Research Fellows. Each fellow will receive two years of funding for research that focuses on the causes of human disease and improved treatment methodologies. Congratulations to all of the awardees!

About the Trust

Established in 1936, the Charles A. King Trust was created to support and promote the investigation of human disease and the alleviation of human suffering through improved treatment. Other contributors, including the Sara Elizabeth O’Brien Trust and Simeon J. Fortin Charitable Foundation, Bank of America, N.A., Trustee, and the Bushrod H. Campbell and Adah F. Hall Charity Fund have joined the Charles A. King Trust, Melissa MacGillivray Dane and Susan Monahan, Co-Trustees, in supporting the King Trust Postdoctoral Research Fellowship Program. The Medical Foundation at Health Resources in Action (HRiA), a non-profit organization in Boston that advances public health and medical research, administers the program on behalf of the Funders.

The Charles A. King Trust Postdoctoral Research Fellowship Program is designed to support postdoctoral fellows and physician-scientists in the mid to late stages of their research training within the state of Massachusetts. The program provides vital support to prepare postdoctoral fellows for academic careers as successful independent investigators in biomedical research through two separate grant programs focused on (1) basic science and (2) clinical and health services research.

More information on the program can be found at: hria.org/tmf/king. Sign up for notifications here. Questions can be emailed to KingAwards@hria.org.

2022 Charles A. King Trust Research Fellows

Khashayar Afshari, M.D., M.P.H.
University of Massachusetts Chan Medical School
Mentor: Mehdi Rashighi, M.D.

Roles of cutaneous T peripheral helper cells as a marker for photosensitivity and disease activity in dermatomyositis

Dr. Afshari will seek to define the underlying mechanisms of photosensitivity and disease pathogenesis in patients with cutaneous Dermatomyositis (DM), an autoimmune disease characterized by skin rash and muscle weakness. Additionally, studies will aim to dissect how skin epithelial and immune cells in DM respond to ultraviolet B exposure and explore novel specific disease markers with potency to be used as therapeutic targets.

 

 


Christiano Alves, Ph.D.
Massachusetts General Hospital
Mentor: Benjamin Kleinstiver, Ph.D.

Development of CRISPR-based genetic cures for spinal muscular atrophy

Dr. Alves will work towards developing strategies to permanently edit the Survival Motor Neuron 2 (SMN2) gene through a one-time CRISPR-based genetic treatment. Success of this project will provide demonstration for the use of CRISPR technologies as a future treatment for Spinal Muscular Atrophy (SMA), the leading genetic cause of infantile death worldwide.

 

 


Arturo Arrona-Palacios, Ph.D.
Brigham and Women’s Hospital
Mentor: Charles Czeisler, Ph.D., M.D.

Project Title: Development of a proteomic biomarker for human circadian timing

Dr. Arrona-Palacios plans to develop and validate a method for measuring internal biological timing in humans. The goal for this project is to develop a robust diagnostic biomarker for circadian timing to improve diagnosis and treatment for patients with circadian rhythm disorders and sleep pathologies and improve personalized medicine.

 

 


Simona Ceglia, Ph.D.
University of Massachusetts Medical School
Mentor: Andrea Reboldi, Ph.D.

A cholesterol byproduct imprints kidney immuno-metabolism in health and disease

Dr. Ceglia will advance our understanding of glomerulonephritis development by investigating the molecular mechanisms underpinning oxysterol production and function in the kidneys. This work may also lead to the identification of oxysterol regulation as a new target for prevention and treatment of IgA nephropathy.

 

 


Stephen Chong, Ph.D.
Dana-Farber Cancer Institute
Mentor: Matthew Davids, M.D., M.M.Sc.

Targeting the phosphorylation Of Bcl-2 family members in venetoclax-resistant lymphoid malignancies

Dr. Chong will determine if lymphoid malignant cells have enhanced phosphorylation of the anti-apoptotic proteins Bcl-2 and Mcl-1 and will test if this modification is the cause of resistance of the FDA-approved drug venetoclax in chronic lymphocytic leukemia.

 

 

 


Alicia Darnell, Ph.D.
Massachusetts Institute of Technology
Mentor: Matthew Vander Heiden, M.D. Ph.D.

Metabolic control of protein synthesis by ribosome stalling

Dr. Darnell will determine the factors that regulate ribosome stalling, which has been linked to neurodegeneration, cancer metastasis, and tumor innervation. This proposal will determine factors that regulate ribosome stalling upon amino acid starvation and identify the consequences of this metabolic form of translational control.

 

 


Sunny Das, Ph.D.
Whitehead Institute for Biomedical Research
Mentor: Robert Weinberg, Ph.D.

Molecular mechanisms of metastatic colonization of the liver by dormant breast cancer cells

Dr. Das will study the transition of disseminated breast cancer cells from dormancy to colonization in the liver which will be further compared with patient datasets to identify potential pharmacological targets. The goal of this work is to ultimately develop anti-metastatic therapies and increase progression free- and overall survival in breast cancer patients.

 

 


Ryan Delgado, M.D. Ph.D.
Harvard Medical School
Mentor: Constance Cepko, Ph.D.

The role of lineage in the temporospatial genesis of retinal bipolar cell subtypes

Dr. Delgado will improve our understanding of retinal development by optimizing and using an “evolvable” lineage tracer he has developed called SCRIBE (Sequential Combinatorial Recorder for Iterative Barcode Evolution) to record patterns of cell division in developing tissue including the retina and determining whether these patterns might underlie proper retinal development.

 

 


Ying Dong, Ph.D.
Boston Children’s Hospital
Mentor: Hao Wu, Ph.D.

Mechanistic elucidation of the B cell receptor (BCR) signaling complex by cryo-EM

Dr. Dong will elucidate the structural assembly of the B cell receptor complex in different conformational states by cryo-electron microscopy and validate the structure using mutagenesis and cell biology. This work will not only provide new insights into B cell signal transduction, but also afford novel therapeutic strategies for the precise treatment of B-cell related diseases.

 

 


Deli Hong, Ph.D.
Dana-Farber Cancer Institute
Mentor: Matthew Oser, M.D., Ph.D.

Dissecting and therapeutically exploiting synthetic lethality between NOTCH and TRIM28 to drive anti-tumor immunity in SCLC

Dr. Hong will study mechanisms underlying NOTCH/TRIM28 synthetic lethality to identify new combination therapeutic strategies to increase immune checkpoint blockade response in small cell lung cancer using genetically engineered mouse models and derived cell lines. If successful, the proposed research could lay the preclinical foundation for a novel therapeutic strategy for the approximately 25% of small cell lung cancer patients that harbor loss-of-function NOTCH mutations.

 

 


Hui Si Kwok, Ph.D.
Harvard University
Mentor: Brian Liau, Ph.D.

Understanding polycomb repressive complex 2 function and dependencies in EZH2-mutant lymphoma using drug addiction alleles

Dr. Kwok will leverage drug resistance and addiction mutations as discovery tools to gain critical understanding into the biology of Polycomb repressive complex 2 (PRC2), provide insight into how other PRC2 cancer mutations might likewise operate, and identify new cancer vulnerabilities.

 

 

 


Ding Liu, Ph.D.
Harvard University
Mentor: Catherine Dulac, Ph.D.

Molecular, circuit and sensory control of the instinctive need for social interactions

Dr. Liu aims to investigate the neurobiological mechanisms underlying social need. Using cutting edge single-cell RNA sequencing, viral tracing, and optogenetic and behavioral assays, this work will assess and compare the molecular, neural circuit, and sensory characteristics across mouse strains to deepen the understanding of the neural basis of social need and provide new insights into the treatment of social isolation induced mental disorders.

 

 


Ane Martin Anduaga, Ph.D.
Brandeis University
Mentor: Sebastian Kadener, Ph.D.

Elucidating the role of timeless thermosensitive alternative splicing in temperature compensation

Dr. Martin Anduaga will elucidate the mechanisms by which temperature compensation of the circadian clock is achieved in eukaryotes. Using molecular and genetic approaches the current proposal seeks to examine this mechanism through determining the contribution of the thermosensitively-regulated isoform of the gene timeless (TIMCOLD) and three TIM isoforms of this locus in temperature compensation.

 

 


Tadasu Nozaki, Ph.D.
Harvard University
Mentor: Nancy Kleckner, Ph.D.

Molecular and physical mechanisms of homolog pairing in meiotic budding yeast

Dr. Nozaki will study how meiotic chromosomal homolog pairing occurs to further inform how failures in pairing lead to aneuploidy or genetic diseases. Utilizing an imaging technology that enables 4D tracking, this work will elucidate the molecular mechanisms of a new process called rapid homolog juxtaposition and the basis and relationship between intra-chromosomal synchrony and longitudinal compaction.

 

 


Sneha Rath, Ph.D.
Massachusetts General Hospital
Mentor: Vamsi Mootha, M.D.

A systems approach to discover sensors and regulators of mitochondrial genome ploidy

Dr. Rath will leverage bioenergetics, high-throughput genetics, and systems approaches to gain fundamental insight into how cells couple their fitness to mitochondrial genome (mtDNA) abundance and regulate their mtDNA copy number. This work has the potential to illuminate new therapeutic targets and accelerate our search for treatments of both inherited and age-associated mtDNA depletion.

 

 


Stefanie Schmieder, Ph.D.
Boston Children’s Hospital
Mentor: Wayne I. Lencer, M.D.

A multiscale approach to study the role of sphingolipids in plasma membrane function and as sensors in innate host defense

Dr. Schmieder will define how nanodomains in epithelial plasma membranes can transmit signals and elucidate how epithelial cells adapt nanodomain function to defend against pathogen invasion at the host-environment interface using a unique structural lipid library in combination with a high-throughput screen. This project will improve understanding of how microbial danger can be innately sensed by plasma membrane dysfunction and transmitted to induce a protective response.

 

 


Rajae Talbi, Ph.D.
Brigham and Women’s Hospital
Mentor: Victor Navarro, Ph.D.

Deciphering the female-specific hypothalamic pathway underlying the metabolic regulation of fertility by the melanocortin receptor 4

Dr. Talbi will study reproductive impairment and characterize a novel sex-dependent hypothalamic pathway in the metabolic control of ovulation by melanocortins using genetic mouse models, viral/pharmacological approaches, and neuroscience techniques. Results from this study will offer new insight and lead to significant clinical improvement of fertility in patients with metabolic disorders.

 

 


Ana Uzquiano Lopez, Ph.D.
Harvard University
Mentor: Paola Arlotta, Ph.D.

Mechanisms governing neuronal population size and identity in the human brain

Dr. Uzquiano Lopez will leverage stem cell-derived brain organoids and genetic tools to investigate how the relative proportions of different neuronal populations are established in the cortex, and to discover the mechanisms that contribute to callosal projection neuron expansion and diversification. This work will shed light on fundamental processes underlying human cerebral cortex assembly, which has enabled major evolutionary adaptations of the human brain.

 

 


Xiaozhe Xiong, Ph.D.
Boston Children’s Hospital
Mentor: Min Dong, Ph.D.

Insight into a novel enterococcus pore-forming toxin family

Dr. Xiong will study the colonization and pathogenesis of Enterococcus by determining whether the uncharacterized family of Enterococcus pore-forming toxins (Epx) are active toxins specifically targeting human cells, what their host factors are, and explore the physiological functions of Epxs during the pathogenesis process using structural analysis of Epxs, genome-wide CRISPRCas9 screens, and animal infection models.

 

 


Xingjie Zhang, Ph.D.
Beth Israel Deaconess Medical Center / Harvard Medical School
Mentor: Mark Andermann, Ph.D.

Competing effects of AgRP and POMC neurons on cAMP signaling in downstream neurons in vivo

Dr. Zhang will apply a recently developed molecular and optical toolset to monitor and manipulate biochemical signaling pathways in mice to understand the how neurons use peptides to communicate with downstream circuits and process hunger and satiety signals. Insights from this work will help fill a substantial knowledge gap in developing treatments for obesity.

 

 


Yang Zhang, Ph.D.
Joslin Diabetes Center
Mentor: Yu-Hua Tseng, Ph.D.

Histone variant H2A.Z-mediated chromatin organization regulates brown adipocyte thermogenic function

Dr. Zhang will study how the histone variant H2A.Z regulates thermogenic gene expression and controls brown adipose tissue activity in human and mouse models. This work has the potential to pave the way for development of new therapeutic approaches to enhance the activity of thermogenic adipocytes to combat obesity and related metabolic disorders such as type 2 diabetes and cardiovascular disease.