People at The Letai Lab
We are a passionate and unique group of scientists, coming from all around the world, as seen in our lab family map! We are joined together by our common goal of improving patient treatment through BH3 mimetics.
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LAB PRINCIPAL INVESTIGATOR
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Tony Letai is a professor in Medicine at Harvard Medical School and Dana Farner Cancer Institute.
He received his MD and PhD at the University of Chicago. His PhD was done under the supervision of Elaine Fuchs. His thesis examined the role of point mutations in keratin proteins in heritable blistering diseases. Dr. Letai then completed clinical training in Internal Medicine at Brigham and Women's Hospital followed by a fellowship in Hematology and Oncology at Dana-Farber Cancer Institute. He was introduced to apoptosis and BCL-2 family proteins as a post-doctoral researcher in the laboratory of the late Stanley Korsmeyer. His laboratory has studied how apoptosis can be evaded, particularly in cancer cells, and how this evasion may be detected and targeted. Key to these studies is a novel assay - BH3 profiling. The laboratory will be testing whether BH3 profiling can be used as a predictive biomarker in clinical cancer therapy. In his free time, Dr. Letai likes to play soccer, tennis, music, and hang around the house to irritate his lovely wife, three kids, and dog. |
Lab Members
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Danielle Potter, Post Doctoral Fellow: I joined the Letai lab after gaining my PhD from the Cancer Research UK Manchester Institute at The University of Manchester. I was previously working in Professor Caroline Dive’s lab on rational drug combinations in the treatment of colorectal and small cell lung cancer. Specifically I was investigating mechanisms to increase the potency of BH3 mimetics which target the Bcl-2 family of proteins which regulate intrinsic apoptosis.
In the Letai Lab, I am interested in investigating whether BH3 profiling can be used to identify patient tumor heterogeneity and whether dynamic BH3 profiling on patient biopsies can be used to aid therapeutic decisions. Also I would like to investigate whether BH3 profiling is possible on circulating tumor cells and what this may reveal about the patient and possible treatment options. I am from Manchester in England which is a great city (I encourage all to visit) but I am excited to be now living in the vibrant city of Boston. I am just finding my way in Boston so in my spare time I am mostly exploring the city and figuring out what other great places I can visit in the states. |
B.A. Chemistry and Biology, 2003, St. Mary’s College of Maryland
S.M. Chemistry, 2005, Massachusetts Institute of Technology Jeremy_Ryan@dfci.harvard.edu PUBMED |
Jeremy Ryan, Staff Scientist: I started in the Letai lab as a technician in 2006, and since then I have been responsible for many of the techniques used by the lab. I find method development interests me most, and I am fortunate to be trusted with our flagship method, BH3 profiling. Having converted the initial ELISA-based method to quick and relatively simple protocols to use membrane potential or cytochrome c retention, our newest methods can be used on small samples from patients so that we might be able to understand not only tumor biology but better direct therapy.
Outside of the lab, I love wildlife photography, music, drawing, and story writing. |
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Rongqing 'Aaron' Pan, Post-Doctoral Fellow: I joined the Letai lab after completing my PhD in Cancer Biology at MD Anderson Cancer Center. My dissertation research focuses on targeting mitochondrial apoptotic pathways and overcoming cancer cell resistance. We demonstrate that targeting mitochondrial apoptosis is an effective approach to kill resistant tumor bulk cells and stem cells (Pan, et al., Cancer Discovery 2014; Pan, et al, Blood 2015). Our work demonstrates that AML cells are dependent on Bcl-2 for survival, which forms the basis for a multi-center trial of ABT-199/venetoclax in relapsed and refractory AML.
In a following project (Pan, et al., Cancer Cell 2017), We demonstrate that resistance to Bcl-2 inhibition can result from acute induction of Mcl-1 or chronic upregulation of Mcl-1, but p53 activation can effectively overcome Mcl-1-mediated resistance. Mechanistically, p53 activation regulates MAPK/GSK3 signaling to regulate Mcl-1 phosphorylation and promote its proteasomal degradation. Surprisingly, we find that p21 (highly induced upon p53 activation) triggers reversible G1-arrest to protect cancer cells from apoptosis. Nevertheless, Bcl-2 inhibition can overcome this resistance by switching the cellular outcomes of p53 activation from pro-survival G1-arrest to apoptosis. Taken together, Bcl-2 inhibition and p53 activation reciprocally overcome leukemia resistance to either strategy alone. The combinatorial strategy also has unprecedented efficacy in several mouse models of drug resistance and has been translated into a phase II trial at 19 cancer centers in US, Canada, France, and Italy. Immune system is a powerful arsenal to fight against cancers. There are several intriguing overlaps between cancer immunotherapy and targeting mitochondrial apoptosis. Here lies my interest and I believe that combining these two emerging therapeutic approaches, that potentially complement each other, holds great promise for cancer treatment. In my spare time, I enjoy running, cooking, good music, movies, and most importantly, playing Ping Pong |
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Salma Parvin, Post-Doctoral Research Fellow: I joined Letai lab in 2017. I am developing high-throughput functional assays to assign novel therapies for Relapsed/Refractory Chronic Lymphocytic leukemia by targeting BCL-2 family proteins.
In free time, I enjoy binge-watching, cooking, painting, exploring different restaurants in Boston and spending time with my husband. |
University of Calcutta, BSc and MSc
University of Miami, Miller School of Medicine, PhD
Salma_parvin@dfci.harvard.edu
PUBMED
University of Miami, Miller School of Medicine, PhD
Salma_parvin@dfci.harvard.edu
PUBMED
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Stephan Bohl, Research Fellow: After finishing my residency at the University Hospital of Ulm, I had the opportunity to spend more time in the lab of Dr. Kroenke focusing on multiple myeloma drug resistance. Since primarily coming from a genetic research background I find it really interesting investigating the link between genetic/epigenetic aberrations and programmed cell death. So I am currently focusing on the role of mitochondrial guided cell death in myeloid malignancies.
Outside of the lab I am enjoying life with my family by either hiking/biking in the nature of New England or exploring the cultural life of Boston. |
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Julie MacDonald, Post-Doctoral Research Fellow:
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Aditi Aryal, Research Technician/Operations Coordinator: I joined the Letai Lab in October 2019, where I first worked with Dr Alex Pourzia studying the mechanism of CAR T cell killing primarily from an apoptotic pathway lens. After her graduation, I moved to Dr Salma Parvin's project where I conduct high throughput DBP on CLL cells to find potential therapeutic hits. I also manage the daily functions of the lab as part of my coordinator role and organize the Society for Functional Precision Medicine's Seminar Series and oversee its membership expansion.
Outside of work, I like photography, new cuisines and history! Smith College, Bachelor's Degree Aditi_Aryal@DFCI.HARVARD.EDU |
Laboratory for Functional Precision Medicine (LFPM)
Given the rapid development of new small molecule cancer therapeutics, there is a growing need for predictive diagnostics to match cancer patients with optimal therapies. Unfortunately, molecular changes induced by cancer therapies are complex, and for most patients we cannot accurately predict tumor response based on pretreatment genomic or proteomic measurements. We previously developed a precision medicine technology with a functional phenotypic readout called dynamic BH3 profiling (DBP). DBP exposes cancer cells to drugs and measures induction of apoptotic cell death signaling after 24 hours ex vivo. We previously performed proof of principle tests using large excisional tumor samples and demonstrated that DBP predicts chemotherapy response in animal models and humans.
The Laboratory for Functional Precision Medicine (LFPM) is a small lab space within the Laboratory for Systems Pharmacology to perform dynamic BH3 Profiling. The goal is to use dynamic BH3 Profiling for identifying drug treatments for cancer types (with a focus on solid tumors), and for precision medicine:
The Laboratory for Functional Precision Medicine (LFPM) is a small lab space within the Laboratory for Systems Pharmacology to perform dynamic BH3 Profiling. The goal is to use dynamic BH3 Profiling for identifying drug treatments for cancer types (with a focus on solid tumors), and for precision medicine:
- HT-DBP screens on colon cancer, pancreatic cancer, fibrolamellar hepatocellular carcinoma, sarcoma, ovarian cancer, rapid autopsy tumors, and canine cancers.
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Patrick Bhola, Instructor at DFCI and Co-Director of the LFPM: Patrick Bhola joined the Letai Lab in 2010 after completing a PhD at Rockefeller University. Patrick studies apoptotic heterogeneity within tumors, and has developed high-throughput approaches to evaluate chemicals that sensitize tumors for apoptosis. In his spare time, Patrick enjoys going to baseball games, aimlessly driving along the seacoast, and spending time with his wife and son.
University of Toronto, BASc Rockefeller Univeristy, PhD Patrick_Bhola@dfci.harvard.edu PUBMED |
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Kelley McQueeney, Post Doctoral Research Fellow: I joined the Letai lab in 2018 after completing my Ph.D. in pharmacology at the University of Virginia. I am using a high throughput image-based assay to determine apoptotic priming in tumor cells. I then use this information to identify compounds that push these tumor cells closer to the apoptotic threshold.
In my free time, I enjoy hiking, watching college football (Go Tigers!), cooking, reading, and exploring all that Boston has to offer. Clemson University, BS University of Virginia, PhD KelleyE_McQueeney@dfci.harvard.edu |
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Atreyi Mukherji, Research Technician: I joined the Letai Lab in December 2019. Here, I work with Dr. Patrick Bhola and study apoptotic heterogeneity within tumors using Real Time-Dynamic BH3 Profiling assay, and analyze molecular features in primed and unprimed cell. In my leisure time, I love cooking new recipes, watching sports, reading, and swimming!
University of Massachusetts, Bachelor's degree atreyi_mukherji@dfci.harvard.edu |
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Emmalyn Lecky, Research Technician: I joined the Letai Laboratory in June 2020 after graduating from the University of Connecticut. Here, I work with Dr. Patrick Bhola in the Laboratory for Functional Precision Medicine, where we use high-throughput dynamic BH3 profiling to screen for compounds that sensitize tumor cells for apoptosis. In my free time I enjoy running, reading, trying new recipes, and exploring the Boston area!
University of Connecticut, Bachelor's Degree Emmalyn_Lecky@DFCI.HARVARD.EDU |