All Cancers

Current Projects
Jose M. Ordovas-Montanes, PhD

Dr. Ordovas-Montanes studies how inflammation in the gut influences individual epithelial and immune cells. Inflammation is one of the largest risk factors for developing colon cancer. A better understanding of the cellular factors involved in precipitating malignancy may lead to novel approaches for blocking the initiation of cancer and restoring the gut to a healthy balanced state.

Project title: "Single-cell genomic approaches for tracing the contribution of inflammation to human colon cancer"
Institution: Massachusetts Institute of Technology
Named Award: HHMI Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Alex Shalek, PhD
Cancer Type: Colorectal, All Cancers
Research Area: Basic Immunology
Bradley L. Pentelute, PhD

Antibodies have proven to be powerful tools in cancer research, facilitating the elucidation of disease mechanisms and generating novel and effective anti-cancer therapeutics. However, antibody biotechnology is limited by one major factor: the inability of antibodies to effectively cross the cell membrane to reach the inside of the cell, or cytosol. A new strategy is clearly necessary-one based on facile and reliable delivery of active antibody-like molecules into various cell types. 

Dr. Pentelute plans to construct a new, targeted delivery platform capable of introducing stable molecules that mimic antibodies (deemed "intrabodies"). He will use this proposed delivery platform to strike the intracellular cancer target Bcr-Abl for treatment of chronic myeloid leukemia. He also aims to target the cancer-promoting complex p53/MDM2 in cancer cells. Through these innovative studies, he aims to advance the frontier by delivering a diverse array of antibody-like molecules into cells for cancer therapy. 

 

Project title: "Striking cancer with intracellular antibodies"
Institution: Massachusetts Institute of Technology
Award Program: Innovator
Cancer Type: All Cancers
Research Area: Chemical Biology
Magdalena E. Potok, PhD

Dr. Potok [HHMI Fellow] is investigating how gene expression is controlled by heterochromatin (the physically compacted form of DNA) and genomic instability. In the plant Arabidopsis thaliana, reduction in a chemical mark on the chromatin, called H3K27me1, results in heterochromatin decompaction, abnormal gene expression and the production of extra DNA from certain regions. Extra copies of DNA are a sign of genomic instability often observed in cancers. She will characterize the mechanism underlying genomic instability. The results of this study may add insight into the connection between epigenetic gene silencing, nuclear architecture, and genome stability, leading to an understanding of why they are misregulated in cancer.

Project title: "The relationship between epigenetic gene silencing, nuclear architecture, and genome stability"
Institution: University of California, Los Angeles
Named Award: HHMI Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Steven E. Jacobsen, PhD
Cancer Type: All Cancers
Research Area: Epigenetics
Guillem Pratx, PhD

Many studies have shown that the cancer cells within a tumor form a remarkably diverse population. These cellular differences play a significant role in how the tumor develops and how it responds to therapy. A technology called flow cytometry (a high-throughput method for characterizing single cells) has been critical for these findings; however, the technology is inherently limited because it can only measure biochemical processes that can be interrogated using a fluorescent molecule.

Dr. Pratx, an engineer by training, is developing a novel method that would enable flow cytometry to measure single cell uptake of any non-fluorescent molecule. This challenging feat will be accomplished by exploiting the fact that molecules can be labeled by radioisotopes. This new tool could transform the ability to study normal and abnormal molecular processes in single cancer cells by allowing flow cytometry to interrogate a much wider range of biomolecules, with high throughput and high temporal resolution.

 

Project title: "Adding a new dimension to flow cytometry: radionuclide-activated cell sorting"
Institution: Stanford University
Award Program: Innovator
Cancer Type: All Cancers
Research Area: Biomedical Engineering
William Razzell, PhD

Dr. Razzell [HHMI Fellow] is using cell biological, molecular genetic, and biophysical approaches to understand how cell-derived mechanical forces contribute to tumorigenesis through the modulation of cellular signaling pathways. One pathway that is responsive to mechanical forces is the Hippo pathway, which prevents excessive tissue growth during development. Characterizing how cell-derived forces control normal Hippo signaling will provide insight into the mechanisms by which Hippo pathway misregulation contributes to tumor progression.

Project title: "The role of tension in Hippo pathway signaling"
Institution: Memorial Sloan Kettering Cancer Center
Named Award: HHMI Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Jennifer A. Zallen, PhD
Cancer Type: Blood, All Cancers
Research Area: Developmental Biology
Alistair B. Russell, PhD

Dr. Russell [Merck Fellow] is investigating the mechanisms by which cells recognize influenza infection. Yearly influenza epidemics present an ongoing medical challenge, and those suffering from cancer are at a potentially increased risk of complication following infection. By identifying both cell-to-cell differences in the response to viral infection and virus-to-virus differences in the capacity to evade the host response, he hopes to develop a better understanding of the kinetics of initial infection and disease progression in individuals.

Project title: "Impact of heterogeneity on the cellular recognition of influenza infection"
Institution: Fred Hutchinson Cancer Research Center
Named Award: Merck Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Jesse D. Bloom, PhD
Cancer Type: All Cancers
Research Area: Virology
Jens C. Schmidt, PhD

The telomerase enzyme adds repetitive DNA sequences to the ends of human chromosomes, assuring genome integrity and providing unlimited proliferative potential to continuously dividing cells. Importantly, 90% of all cancers require telomerase activity for their survival. Mutations that activate the expression of telomerase reverse transcriptase (TERT), the major protein subunit of telomerase, are the most frequent mutations in a number cancers and are strongly correlated with poor clinical outcomes for patients carrying them. Telomerase is therefore an attractive target to potentially treat a wide range of aggressive cancers. Dr. Schmidt has developed techniques to study telomerase trafficking in vivo, as well as single-molecule assays to analyze telomerase catalysis and its modulation in vitro. He is able to visualize enzymatic action of telomerase in real-time at nucleotide resolution. He aims to understand the enzymatic mechanism of telomerase catalysis to identify potential weaknesses that can be targeted to inhibit telomerase action in cancer cells.

Project title: "Single molecule analysis of telomerase recruitment to telomeres"
Institution: University of Colorado
Award Program: Dale Frey Scientist
Cancer Type: All Cancers
Research Area: Biochemistry
Esen Sefik, PhD

Dr. Sefik is examining the connection between obesity, cancer and the microbiome. An estimated 600 million people worldwide suffer from obesity, with 15-20% of deaths from cancer in the US alone linked to obesity. Recent studies in mice highlight the importance of intestinal bacteria and immune cells in obesity and colorectal cancer; however, these roles are not yet well characterized in humans. She will   analyze how high fat diet and obesity-associated intestinal bacteria change intestinal immunity in mice that harbor the human immune system and the human microbiota. This will help resolve some of the existing discrepancies and discover new players that are relevant to obesity and cancer in humans and help engineer better-targeted, combined therapies to colorectal cancer, especially in cases where existing immunotherapy fails.

Project title: "The effect of microbes, diet on the intestinal immune system in the context of obesity and cancer"
Institution: Yale University
Named Award: HHMI Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Richard A. Flavell, PhD
Cancer Type: Colorectal, All Cancers
Research Area: Basic Immunology
Agnel Sfeir, PhD

Each cell contains organelles called mitochondria, which are the powerhouses of cells, producing energy in the form of ATP. Mitochondria contain their own separate DNA, which codes for key energy-producing enzymes. Maintaining the integrity of the mitochondrial genome is necessary for optimal cellular function and for protection against diseases. Alterations in mitochondrial DNA are associated with and can promote metastasis of many tumors, such as lung, breast and prostate. Such aberrations range from single base substitutions to large-scale deletions that remove segments of the mitochondrial genome. The mechanism by which these aberrations influence disease progression remains unclear. 

Dr. Sfeir aims to uncover the underlying basis for accumulation of these highly dangerous deletions in mitochondrial DNA and the mechanism by which they shape tumor behavior. This work will help identify novel strategies to preserve mitochondrial function and thwart tumor progression.

Project title: "Pathways involved in preserving the genomic stability of mitochondrial DNA"
Institution: New York University School of Medicine
Award Program: Innovator
Cancer Type: All Cancers
Research Area: Cancer Genetics
Jianjin Shi, PhD

Dr. Shi [Layton Family Fellow] is exploring how cells die in the nervous system in both healthy and disease states. He will focus on a novel and ill-defined form of cell death in the nerve cells and nerve fibers upon injury or stress. Resisting cell death is a hallmark of all cancers. Furthermore, many cancer chemotherapeutic drugs cause the death of nerve cells and nerve fibers, therefore inducing neurological diseases in cancer patients. Using multiple state-of-the-art approaches, he aims to find the unknown components and molecular mechanisms of this type of cell death which will not only identify new drug targets for cancer treatments, but also shed light on how to reduce some side effects of chemotherapy.

Project title: "Biochemical and genetic dissection of axon degeneration"
Institution: Stanford University
Named Award: Layton Family Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Marc Tessier-Lavigne, PhD
Cancer Type: All Cancers
Research Area: Cell Death
  • You can support our innovative researchers.