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WELCOME TO THE

JOSHI LAB

 

Half of all men and one-third of all women will get cancer in their lifetime

This sobering statistic underscores the importance of cancer in human health. Sadly, for those who get cancer, nearly half will die from their disease. Worse, despite the best efforts of thousands of researchers and billions of dollars spent, finding a cure for cancer has always felt more like a dream than reality. Thus, cancer patients and their families were left with toxic treatments that provided short term solutions, but rarely led to cures. 

The immune revolution in cancer

In the past few years, there has been a revolution in cancer therapy following the demonstration that cells of the immune system can be used to fight cancer. The key to this discovery was the realization that in many patients with tumors, they have immune cells that are naturally fighting cancer. Many patients already have immune cells inside them that can completely destroy their cancer, but not without help. New "immunotherapeutics" (drugs that target the immune system) have been developed to help the natural immune system to find and destroy the cancer in the body. Amazingly, when these therapies are successful, patients can be cleared of multiple tumors, throughout the body, and more impressively, they can remain tumor-free for decades without further treatment. Because they target the immune system, immunotherapeutics have been successful in many different types of cancer, and while the trials are too recent to know how many patients will survive long term, the data suggest that patients who do not relapse within 3 years will remain tumor-free and are functionally cured of their disease. Thus, unlike other therapies, immunotherapeutics have the potential to cure types of cancer. This realization has electrified the oncology field and led to cancer immunology being named the scientific breakthrough in 2013 by Science Magazine.

Helping more patients

Despite the amazing results seen with immunotherapeutics, there are still only some patients that benefit from treatment and it's not clear why that is. This is a complex problem because the failures happen in patients, where data is difficult to obtain. Furthermore, it is not clear why immune cells naturally recognize tumors, but cannot destroy them without help in patients with cancer.  Finally, we don't know much about the immune cells that fight cancer, and therefore it is hard to know how to fix them in cancer patients. Our goal in the lab is to figure out how cancer and the immune system interact during the development of cancer to understand why the natural immune response against cancer fails and to figure out how new ways for we can improve that response. 

Lab Phone

(203) 785 -4466

 

Lab Location

The Anlyan Center S540                       

Yale University

 

Team


 
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Nikhil Joshi Ph.D.

Principle Investigator

 

 

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Diane Trotta

Research Associate

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Mursal Nader

Postgraduate Associate

 

 

 

 

 

 

 

 

Brittany Fitzgerald

Graduate Student

 

 

 

 

 

 

 

 

Martina Damo

Postdoctoral Associate

 

 

 

 

 

 

 

 

 

 

Peter Fowles

Research Associate

 

 

 

 

 

 

 

Mihir Khunte

Undergraduate Student

 

 

 

 

 

 

Darwin Kwok

Postgraduate Associate

 

 

 

 

 

 

 

Gene Yoo

Medical Student

 

all Publications

 

Tammela T, Sanchez-Rivera FJ, Cetinbas NM, Wu K, Joshi NS, et al. A Wnt-producing niche drives proliferative potential and progression in lung adenocarcinoma. Nature. 2017 May 18;545(7654):355-359. PubMed PMID: 28489818.

Xin G, Schauder DM, Jing W, Jiang A, Joshi NS, et al. Pathogen boosted adoptive cell transfer immunotherapy to treat solid tumors. Proc Natl Acad Sci U S A. 2017 Jan 24;114(4):740-745. PubMed PMID: 28069963; PubMed Central PMCID: PMC5278465.

Adams NM, O'Sullivan TE, Geary CD, Karo JM, Amezquita RA, et al. NK Cell Responses Redefine Immunological Memory. J Immunol. 2016 Oct 15;197(8):2963-2970. PubMed PMID: 27824591; NIHMSID: NIHMS800172; PubMed Central PMCID: PMC5108457.

Akama-Garren EH*, Joshi NS*, Tammela T, Chang GP, Wagner BL, et al. A Modular Assembly Platform for Rapid Generation of DNA Constructs. Sci Rep. 2016 Feb 18;6:16836. PubMed PMID: 26887506; PubMed Central PMCID: PMC4757859.

Dominguez CX, Amezquita RA, Guan T, Marshall HD, Joshi NS, et al. The transcription factors ZEB2 and T-bet cooperate to program cytotoxic T cell terminal differentiation in response to LCMV viral infection. J Exp Med. 2015 Nov 16;212(12):2041-56. PubMed PMID: 26503446; PubMed Central PMCID: PMC4647261.

Joshi NS, Akama-Garren EH, Lu Y, Lee DY, Chang GP, et al. Regulatory T Cells in Tumor-Associated Tertiary Lymphoid Structures Suppress Anti-tumor T Cell Responses. Immunity. 2015 Sep 15;43(3):579-90. PubMed PMID: 26341400; NIHMSID: NIHMS769682; PubMed Central PMCID: PMC4826619. 

Sánchez-Rivera FJ, Papagiannakopoulos T, Romero R, Tammela T, Bauer MR, et al. Rapid modelling of cooperating genetic events in cancer through somatic genome editing. Nature. 2014 Dec 18;516(7531):428-31. PubMed PMID: 25337879; NIHMSID: NIHMS633102; PubMed Central PMCID: PMC4292871.

Xue W, Chen S, Yin H, Tammela T, Papagiannakopoulos T, et al. CRISPR-mediated direct mutation of cancer genes in the mouse liver. Nature. 2014 Oct 16;514(7522):380-4. PubMed PMID: 25119044; NIHMSID: NIHMS606316; PubMed Central PMCID: PMC4199937.

Cui W, Joshi NS, Liu Y, Meng H, Kleinstein SH, et al. TLR4 ligands lipopolysaccharide and monophosphoryl lipid a differentially regulate effector and memory CD8+ T Cell differentiation. J Immunol. 2014 May 1;192(9):4221-32. PubMed PMID: 24659688; NIHMSID: NIHMS570384; PubMed Central PMCID: PMC4071140.

Drake A, Joshi NS, Szeto GL, Zhu E, Eisen HN, et al. Koch Institute Symposium on Cancer Immunology and Immunotherapy. Cancer Immunol Res. 2013 Oct;1:217-222. PubMed PMID: 24466562; NIHMSID: NIHMS525722; PubMed Central PMCID: PMC3897860.

Joshi NS, Jacks T. Immunology Guilty by association. Science. 2013 Mar 8;339(6124):1160-1. PubMed PMID: 23471395.

Joshi NS, Cui W, Dominguez CX, Chen JH, Hand TW, et al. Increased numbers of preexisting memory CD8 T cells and decreased T-bet expression can restrain terminal differentiation of secondary effector and memory CD8 T cells. J Immunol. 2011 Oct 15;187(8):4068-76. PubMed PMID: 21930973; NIHMSID: NIHMS319679; PubMed Central PMCID: PMC3991478. 

Jung YW, Rutishauser RL, Joshi NS, Haberman AM, Kaech SM. Differential localization of effector and memory CD8 T cell subsets in lymphoid organs during acute viral infection. J Immunol. 2010 Nov 1;185(9):5315-25. PubMed PMID: 20921525; NIHMSID: NIHMS343065; PubMed Central PMCID: PMC4267692.

Hand TW, Cui W, Jung YW, Sefik E, Joshi NS, et al. Differential effects of STAT5 and PI3K/AKT signaling on effector and memory CD8 T-cell survival. Proc Natl Acad Sci U S A. 2010 Sep 21;107(38):16601-6. PubMed PMID: 20823247; PubMed Central PMCID: PMC2944719.

Hinson ER*, Joshi NS*, Chen JH, Rahner C, Jung YW, et al. Viperin is highly induced in neutrophils and macrophages during acute and chronic lymphocytic choriomeningitis virus infection. J Immunol. 2010 May 15;184(10):5723-31. PubMed PMID: 20410488; NIHMSID: NIHMS526962; PubMed Central PMCID: PMC3883313.

Cui W, Joshi NS, Jiang A, Kaech SM. Effects of Signal 3 during CD8 T cell priming: Bystander production of IL-12 enhances effector T cell expansion but promotes terminal differentiation. Vaccine. 2009 Mar 26;27(15):2177-87. PubMed PMID: 19201385; NIHMSID: NIHMS103971; PubMed Central PMCID: PMC2803112.

Chandele A, Joshi NS, Zhu J, Paul WE, Leonard WJ, et al. Formation of IL-7Ralphahigh and IL-7Ralphalow CD8 T cells during infection is regulated by the opposing functions of GABPalpha and Gfi-1. J Immunol. 2008 Apr 15;180(8):5309-19. PubMed PMID: 18390712; NIHMSID: NIHMS144818; PubMed Central PMCID: PMC2792750.

Joshi NS, Kaech SM. Effector CD8 T cell development: a balancing act between memory cell potential and terminal differentiation. J Immunol. 2008 Feb 1;180(3):1309-15. PubMed PMID: 18209024.

Joshi NS, Cui W, Chandele A, Lee HK, Urso DR, et al. Inflammation directs memory precursor and short-lived effector CD8(+) T cell fates via the graded expression of T-bet transcription factor. Immunity. 2007 Aug;27(2):281-95. PubMed PMID: 17723218; NIHMSID: NIHMS29566; PubMed Central PMCID: PMC2034442. 

Tesar BM, Walker WE, Unternaehrer J, Joshi NS, Chandele A, et al. Murine [corrected] myeloid dendritic cell-dependent toll-like receptor immunity is preserved with aging. Aging Cell. 2006 Dec;5(6):473-86. PubMed PMID: 17129212.

Martomo SA, Fu D, Yang WW, Joshi NS, Gearhart PJ. Deoxyuridine is generated preferentially in the nontranscribed strand of DNA from cells expressing activation-induced cytidine deaminase. J Immunol. 2005 Jun 15;174(12):7787-91. PubMed PMID: 15944282.

Henry RM, Hoppe AD, Joshi N, Swanson JA. The uniformity of phagosome maturation in macrophages. J Cell Biol. 2004 Jan 19;164(2):185-94. PubMed PMID: 14718518; PubMed Central PMCID: PMC2172341.

Select Publications

Click on the images to access PDF files of some of our select publications

Joshi et al. 2015

Joshi et. al. Immunity 2007 

Akama-Garren et al. 2016

Joshi et. al. J immunol 2011

Hinson et. al. J Immunol 2010