Lestat Ali

Computational Immunologist & Resident Physician

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My career started in earnest in 2011 as a software engineer at Apple before I pivoted to focus my computational skills on applications that I felt more passionate about in the biomedical world. I joined Stephanie Dougan’s research laboratory at the Dana-Farber Cancer Institute in 2016 and have been working since then on solving interesting questions about cancer immunotherapy. I do this most by analyzing single-cell RNA sequencing data from people (and sometimes mice) with cancer. At the same time, I have been advancing my clinical training, hoping ultimately to lead a career of concerted patient care and research that expands the amazing—but very limited—success of immunotherapy to every single patient with cancer.


Work Experiences

Internal Medicine Resident

Massachusetts General Hospital | 2022 - Present

Rigorous clinical training in internal medicine.

Bioinformatics Analyst

Dana-Farber Cancer Institute | 2016 - Present

Analyzing single-cell RNA sequencing data from patient samples to improve cancer immunotherapy.

Software Engineering Tech Lead

Apple | 2011 - 2016

Served as technical lead for the development of the iPhone operating system.

Manager of E-Commerce

Harvard Student Agencies | 2009 - 2011

Led a team in overhauling the organization’s e-commerce infrastructure.

Publications

Blockade of IL-1β and PD-1 with combination chemotherapy reduces systemic but not intratumoral myeloid suppression in metastatic pancreatic cancer

Cancer Immunology Research | 2024

Oberstein PE, Costa AD*, Kawaler EA*, Cardo-Ruffino V*, Rahma OE, Beri N, Singh H, Abrams T, Biller L, Cleary JM, Enzinger P, Huffman BM, McCleary NJ, Perez KJ, Rubinson DA, Schaletter BL, Surana R, Yurgelun MB, Wang SJ, Remland J, Brais LK, Bollenrucher N, Chang E, Ali LR, Lenehan PJ, Dolgalev I, Werba G, Lima C, Keleher CE, Sullivan K, Dougan M, Hajdu C, Dajee M, Pelletier M, Nazeer S, Squires M, Bar-Sage D, Wolpin BM, Nowak JA*, Simeone DM*, Dougan SK*.
PubMed

Biomarkers of pembrolizumab efficacy in advanced anal squamous cell carcinoma: analysis of a phase II clinical trial and a cohort of long-term responders

Journal for Immunotherapy of Cancer | 2024

Huffman BM, Singh H, Ali LR, Horick N, Wang SJ, Hoffman MT, Metayer KA, Murray S, Bird A, Abrams TA, Biller LH, Chan JA, Meyerhardt JA, McCleary NJ, Goessling W, Patel AK, Wisch JS, Yurgelun MB, Mouw K, Reardon B, Van Allen EM, Zerillo JA, Clark JW, Parikh A, Mayer RJ, Schlechter B, Ng K, Kumar S, Del Vecchio Fitz C, Kuperwasser C, Hanna GJ, Coveler AL, Rubinson DA, Welsh EL, Pfaff K, Rodig S, Dougan SK, Cleary JM.
PubMed

PD-1 blockade induces reactivation of non-productive T cell responses characterized by NF-κB signaling in patients with pancreatic cancer

Clinical Cancer Research | 2023

Ali LR, Lenehan PJ, Cardot-Ruffino V, Costa AD, Katz MHG, Bauer TW, Nowak JA, Wolpin BM, Abrams TA, Patel AK, Clancy TE, Wang J, Mancias JD, Reilley MJ, Stucky CH, Bekaii-Saab TS, Elias R, Merchant N, Slingluff CL, Rahma OE, Dougan SK.
PubMed

PD-1 blockade and CDK4/6 inhibition augment nonoverlapping features of CD8 T cell activation in metastatic breast cancer

Journal of Experimental Medicine | 2023

Ali LR, Garrido-Castro AC, Lenehan P, Bollenrucher N, Stump CT, Dougan M, Goel S, Shapiro GI, Tolaney SM, Dougan SK.
PubMed

cIAP1/2 Antagonism Induces Antigen-Specific T Cell-Dependent Immunity

Journal of Immunology | 2023

Ventre KS, Roehle K, Bello E, Bhiuyan AM, Biary T, Crowley SJ, Bruck PT, Heckler M, Lenehan PJ, Ali LR, Stump CT, Lippert V, Clancy-Thompson E, Alberto WDC, Hoffman MT, Qiang L, Pelletier M, Akin JJ, Dougan M, Dougan SK.
PubMed

Transforming Growth Factor-β Blockade in Pancreatic Cancer Enhances Sensitivity to Combination Chemotherapy

Gastroenterology | 2023

Qiang L, Hoffman MT, Ali LR, Castillo JI, Kageler L, Temesgen A, Lenehan P, Wang SJ, Bello E, Cardot-Ruffino V, Uribe GA, Yan g A, Dougan M, Aguirre AJ, Raghavan S, Pelletier M, Cremasco V, Dougan SK.
PubMed

IFNγ is a central node of cancer immune equilibrium

Cell Reports | 2023

Walsh PJ, Stump CT, Kureshi R, Lenehan P, Ali LR, Dougan M, Knipe DM, Dougan SK.
PubMed

A split, conditionally active mimetic of IL-2 reduces the toxicity of systemic cytokine therapy

Nature Biotechnology | 2023

Quijano-Rubio A, Bhuiyan MA, Yang H, Leung I, Bello E, Ali LR, Zhangxu K, Perkins J, Chun JH, Wang W, Lajoie MJ, Ravichandran R, Kuo YH, Dougan SK, Riddell S, Spangler J, Dougan M, Silva DA, Baker D.
PubMed

Blockade of innate inflammatory cytokines TNFα, IL-1%beta;, or IL-6 overcomes virotherapy-induced cancer equilibrium to promote tumor regression

Immunotherapy Advances | 2023

Walsh PJ, Ali LR, Lenehan P, Kureshi CT, Kureshi R, Dougan M, Knife DM, Dougan SK.
PubMed

Inhibition of CDK4/6 promotes CD8 T cell memory formation

Cancer Discovery | 2021

Heckler M*, Ali LR*, Clancy-Thompson E, Qiang L, Ventre K, Lenehan P, Roehle K, Luoma A, Boelaars K, Peters V, McCreary J, Boschert T, Wang ES, Suo S, Marangoni F, Mempel TR, Long HW, Wucherpfenning KW, Dougan M, Gray NS, Yuan GC, Goel S, Tolaney SM, Dougan SK
PubMed

Tissue eosinophils express the IL-33 receptor ST2 and type 2 cytokines in patients with eosinophilic esophagitis

Allergy | 2021

Uchida AM, Lenehan PJ, Vimalathas P, Miller KC, Valencia-Yang M, Qiang L, Canha LA, Ali LR, Dougan M, Garber JJ, Dougan SK.
PubMed

cIAP1/2 antagonism eliminates MHC class I-negative tumors through T cell-dependent reprogramming of mononuclear phagocytes

Science Translational Medicine | 2021

Roehle K, Qiang L, Ventre K, Heid D, Ali LR, Lenehan P, Heckler M, Crowley SJ, Stump C, Godicelj A, Bhuiyan MA, Yang A, del Rey M, Biary T, Luoma A, Bruck PT, Tegetoff J, Nopper S, Li J, Byrne K, Pelletier M, Wucherpfennig KW, Stanger BZ, Akin J, Macias J, Agudo J, Dougan M, Ro G, Dougan SK.
PubMed

Disagreement in measured neural responses to speech accent is driven by study design and analytical parameters

Scientific Reports | 2021

Strauber CB, Ali LR, Fujioka T, Thille C, McCandliss B.
PubMed

Immune receptor inhibition through enforced phosphatase recruitment

Nature | 2020

Fernandes RA, Su L, Nishiga Y, Ren J, Bhuiyan MA, Cheng N, Kuo CJ, Picton L, Ohtsuki S, Majzner RG, Rietberg SP, Mackall CL, Yin Q, Ali LR, Yang X, Savvides CS, Sage J, Dougan M, Garcia KC.
PubMed

Neoleukin-2 enhances anti-tumor immunity downstream of peptide vaccination targeted by an anti-MHC class II VHH

Open Biology | 2020

Crowley SJ*, Bruck PT*, Bhuiyan MA, Mitchell-Gears A, Walsh MJ, Zhangxu K, Ali LR, Jeong HJ, Ingram JR, Knipe DM, Ploegh HL, Dougan M, Dougan SK.
PubMed

De novo design of potent and selective mimics of IL-2/IL-15

Nature | 2019

Silva DA*, Yu S*, Ulge UY*, Spangler JB*, Jude KM, Labão-Almeida C, Ali LR, Quijano-Rubio A, Ruterbusch M, Leung I, Biary T, Marcos E, Walkey CD, Weitzner BD, Carter L, Stewart L, Riddell S, Pepper M, Bernardes GJL, Dougan M, Garcia KC, Baker D.
PubMed

Transnuclear mice reveal a population of Peyer’s patch iNKT cells that regulate B cell class switching to IgG1.

The EMBO Journal | 2019

Clancy-Thompson E*, Chen GZ*, LaMarche NM, Ali LR, Jeong HJ, Crowley SJ, Boelaars K, Brenner,MB, Lynch L, Dougan SK.
PubMed

Anti–CTLA-4 therapy requires an Fc domain for efficacy

PNAS | 2018

Ingram JR, Blomberg OS, Rashidian M, Ali LR, Garforth S, Fedorov E, Fedorov AA, Bonanno JB, Le Gall C, Crowley S, Espinosa C, Biary T, Keliher EJ, Weissleder R, Almo SC, Dougan SK, Ploegh HL, Dougan M.
PubMed

Altered binding of tumor antigenic peptides to MHC class I affects CD8 T cell effector responses

Cancer Immunology Research | 2018

Clancy-Thompson E, Devlin CA, Tyler PM, Servos MM, Ali LR, Ventre KS, Bhuiyan MA, Bruck PT, Birnbaum M, Dougan SK.
PubMed

Targeting cytokine therapy to the pancreatic tumor microenvironment using PD-L1 specific VHHs

Cancer Immunology Research | 2018

Dougan M*, Ingram JR*, Jeong HJ, Mosaheb MM, Bruck PT, Ali LR, Pishesha N, Blomberg O, Tyler PM, Servos MM, Rashidian M, Nguyen QD, von Andrian UH, Ploegh HL, Dougan SK.
PubMed

IAP antagonists enhance cytokine production from mouse and human iNKT cells

Cancer Immunology Research | 2018

Clancy-Thompson E, Ali LR, Bruck PT, Exley MA, Blumberg RS, Dranoff G, Dougan M, Dougan SK.
PubMed

Localized CD47 blockade enhances immunotherapy for murine melanoma

PNAS | 2017

Ingram JR, Blomberg OS, Sockolosky JT, Ali LR, Schmidt FI, Pishesha N, Espinosa C, Dougan SK, Garcia KC, Ploegh HL, Dougan M.
PubMed

*Contributed equally.

Presentations

Inhibition of CDK4/6 Promotes T-Cell Memory Formation

May 25, 2023

Armstrong Transformation in Medicine Lectures, Massachusetts General Hospital

[Poster] CDK4/6 inhibition augments T cell memory

March 15, 2022

Elizabeth D. Hay Prize for Basic Science Research
Soma-Weiss Research Day, Harvard Medical School

PD-1 blockade and CDK4/6 inhibition augment nonoverlapping features of CD8 T cell activation

March 4, 2022

Department of Immunology Work in Progress, Harvard Medical School

CDK4/6 inhibitors enhance T cell memory formation

July 23, 2021

Agudo Lab, Dana-Farber Cancer Institute

How the Pandemic Affected Medical Education from the Perspectives of Medical Students from Around the Globe

June 17, 2021

Brigham Education Institute, Brigham and Women’s Hospital

CDK4/6 inhibition potentiates CD8 T cell memory in mouse models and human breast cancer patients

June 29, 2020

Ludwig Center, Harvard Medical School

[Poster] Anti-CTLA-4 therapy requires an Fc domain for efficacy

June 19, 2018

Best Poster Prize, Cancer Immunology & Virology Annual Scientific Retreat, Dana-Farber Cancer Institute