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
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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Julie MacDonald, Post-Doctoral Research Fellow:I joined the Letai Lab in 2019 after completing my Ph.D. in the Laboratory for Aging and Infertility Research under Jonathan Tilly and Dori Woods at Northeastern University. My work here seeks to understand how therapy-induced senescence in varied cancer models impacts apoptotic priming, and more broadly how the Bcl-2 family control of apoptosis is impacted by aging.
I also enjoy baking, trying new crafts, playing tennis, and can be frequently found at the Museum of Fine Arts on weekend afternoons. |
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Maria Davern, Post-Doctoral Research Fellow: I joined the Letai lab in November 2021 after completing my PhD in cancer immunology in the Trinity St. James’s Cancer Center in Trinity College Dublin, Ireland (2017-2021). My interest in cancer immunology and targeting programmed cell death pathways to overcome treatment resistance began during my MSc in Translational Oncology, which I carried out in Trinity College Dublin, Ireland (2016-2017). The primary focus of my work here in the Letai lab aims to identify novel combinations of drugs to combine with immunotherapies to prevent tumour recurrence, improving survival outcomes for patients. In my free time I enjoy running, reading, yoga and barre classes.
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Michael Olson, Post-Doctoral Research Fellow
Saurashtra University, BSc
Nottingham Trent University, MRes Helsinki University, PhD disha_malani@dfci.harvard.edu PUBMED |
Disha Malani, Post-Doctoral Research Fellow : I joined the Letai Lab after my PhD in leukemia functional precision medicine in Professor Olli Kallioniemi's group at the Institute for Molecular Medicine Finland (FIMM), University of Helsinki. My persistent interest in functional precision medicine led my research efforts to explore the apoptosis angle for solid tumors in the Letai Lab. I investigate the therapeutic potential of chemical compounds/drugs using imaging-based dynamic BH3 profiling to find the most effective drugs for patients with solid tumors. In addition, I apply different data analysis strategies to define molecular and phenotypic features associated with apoptosis priming, ex vivo drug responses, clinical characteristics and clinical therapy responses.
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Cheyanne Walker-Williams, Research Technician/Operations Coordinator: I joined the Letai Lab in July 2021, where I first worked with Dr Stephan Bohl studying the role that the mitochondrial apoptotic pathway has on myeloid malignancies. Then I transitioned into working with Dr Julie MacDonald researching BCL-2 family proteins in relation to therapy-induced senescence on several cancer models. Now, I work with Dr. Michael Olson on CAR-T Therapies. I also manage the daily functions of the lab as part of my coordinator role.
Outside of work, I like writing poetry, exploring Boston and trying new foods! Smith College, Bachelor's Degree cheyanne_walkerwilliams@dfci.harvard.edu |
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Leah Krotee, Research Technician: I joined the Letai Lab in July 2022. Broadly, my interests are in physiology and human health. I am especially interested in work that has clinical relevance as I have a passion for translational research which is what brought me to the Letai lab. Currently, I am working with Dr. Emma-Jayne Minihane on studying the use of dynamic BH3 profiling in the development of targeted drug therapies for AML patients.
I am from a small rural town in Maryland and am excited to have the opportunity to live in the city and explore all that Boston has to offer! In my free-time I enjoy finding new restaurants to try, watching Netflix, being in nature, and swimming. Dickinson College, Bachelor's Degree Leah_Krotee@DFCI.HARVARD.EDU |
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Emma-Jayne Mihihane, Post Doctoral Researcher: After completing my PhD at the University of Cambridge (Babraham Institute, Dr Simon Cook lab), I joined the Letai lab in August 2020. My PhD research focused on developing optimised combinations of BH3 mimetics with BRAF and/or MEK1/2 inhibitors in melanoma and colorectal cancer, and this is where my interest in precision medicine began. I am now hoping to investigate acquired resistance to BH3 mimetics, and other targeted therapies, in AML with the aim of understanding the mechanisms underpinning the resistance.
I am originally from the small island of Jersey in the Channel Islands so I am excited to now be living in Boston and exploring all that it has to offer. In my spare time I enjoy running, finding new places to explore, portrait sketching, and testing out the local restaurants! University of Cambridge, PhD Emma-Jayne_Minihane@DFCI.HARVARD.EDU |
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Brenda Chan, Research Technician: I joined the Letai lab in May 2022 after working in the Livingston lab for 3 years. I am working with Jeremy Ryan, where we use baseline BH3 profiling on samples from leukemia patients in therapeutic effectiveness and response studies.
In my free time I enjoy working out, cooking, playing ukulele and watching TV shows. UCLA, Bachelor's degree brendac_chan@dfci.harvard.edu |
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Jasmine Kung, Undergraduate researcher: I am an undergraduate student at Harvard studying Molecular and Cellular Biology with a secondary in Economics. I joined the Letai Lab in February 2020 and have been working remotely with Dr. Salma Parvin on identifying chemical vulnerabilities in chronic lymphocytic leukemia (CLL) cells using high-throughput dynamic BH3 profiling. In the future, I hope to attend medical school and to become a pediatric oncologist, while also conducting research focusing on pediatric cancer.
In my free time, I enjoy dancing (ballet, hip-hop, and jazz specifically), exploring new cafes in Cambridge and Boston, and drinking matcha green tea latte! |
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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Gabriella Stone, Research Technician: I joined the Letai Lab in June of 2021. I have been working with Dr. Patrick Bhola to conduct high-throughput dynamic BH3 profiles to screen for chemicals that sensitize cancer cells to apoptosis and analyze cancer cells' apoptotic heterogeneity and the heterogeneity of molecular markers in cancer cells using CyCIF.
When I'm not in the lab, I love to go cycling, learn new piano songs, spend time around animals, and have recently taken up embroidery. Holyoke College, Bachelor's degree GabriellaM_Stone@DFCI.HARVARD.EDU |
Michael Yorsz, Research Technician
Eden Fessesha, Undergraduate Researcher