Image Place holder

Alex Jaeger, PhD

Program: Molecular Oncology

Overview

Dr. Jaeger’s research is focused on understanding the fundamental relationships between gene expression and protein metabolism that shape antigen presentation in the tumor microenvironment. Using inducible affinity tags, Dr. Jaeger is able to isolate tumor specific MHC-I peptides from genetically engineered models of pancreatic and lung adenocarcinomas, using this information to profile the evolution of the immunopeptidome through tumor progression. These approaches will pave the way to new strategies for cancer immunotherapy, including cancer vaccines, tumor targeting antibodies, and adoptive cell therapy. Dr. Jaeger’s work has been published in top-tier journals such as Nature Structural Molecular Biology, Clinical Cancer Research, Cancer Cell and Nature Cancer.


Associations

    • Molecular Oncology
    • Cancer Biology and Evolution Program

Education & Training

Graduate:

  • Duke University School of Medicine - PhD - Pharmacology and Cancer Biology

Fellowship:

  • Massachusetts Institute of Technology, - Biomedical Research
Research

Dr. Jaeger’s research is focused on understanding the fundamental relationships between gene expression and protein metabolism that shape antigen presentation in the tumor microenvironment. Using inducible affinity tags, Dr. Jaeger is able to isolate tumor specific MHC-I peptides from genetically engineered models of pancreatic and lung adenocarcinomas, using this information to profile the evolution of the immunopeptidome through tumor progression. These approaches will pave the way to new strategies for cancer immunotherapy, including cancer vaccines, tumor targeting antibodies, and adoptive cell therapy. Dr. Jaeger’s work has been published in top-tier journals such as Nature Structural Molecular Biology, Clinical Cancer Research, Cancer Cell and Nature Cancer.

Publications

  • Burger ML, Cruz AM, Crossland GE, Gaglia G, Ritch CC, Blatt SE, Bhutkar A, Canner D, Kienka T, Tavana SZ, Barandiaran AL, Garmilla A, Schenkel JM, Hillman M, de Los Rios Kobara I, Li A, Jaeger AM, Hwang WL, Westcott PMK, Manos MP, Holovatska MM, Hodi FS, Regev A, Santagata S, Jacks T. Antigen dominance hierarchies shape TCF1+ progenitor CD8 T cell phenotypes in tumors. Cell. 2021 Sep.184(19):4996-5014.e26. Pubmedid: 34534464. Pmcid: PMC8522630.
  • Nishida Y, Zhao R, Heese LE, Akiyama H, Patel S, Jaeger AM, Jacamo RO, Kojima K, Ma MCJ, Ruvolo VR, Chachad D, Devine W, Lindquist S, Davis RE, Porco JA, Whitesell L, Andreeff M, Ishizawa J. Inhibition of translation initiation factor eIF4a inactivates heat shock factor 1 (HSF1) and exerts anti-leukemia activity in AML. Leukemia. 2021 Sep.35(9):2469-2481. Pubmedid: 34127794. Pmcid: PMC8764661.
  • Westcott PMK, Sacks NJ, Schenkel JM, Ely ZA, Smith O, Hauck H, Jaeger AM, Zhang D, Backlund CM, Beytagh MC, Patten JJ, Elbashir R, Eng G, Irvine DJ, Yilmaz OH, Jacks T. Low neoantigen expression and poor T-cell priming underlie early immune escape in colorectal cancer. Nat Cancer. 2021 Oct.2(10):1071-1085. Pubmedid: 34738089. Pmcid: PMC8562866.
  • Freed-Pastor WA, Lambert LJ, Ely ZA, Pattada NB, Bhutkar A, Eng G, Mercer KL, Garcia AP, Lin L, Rideout WM, Hwang WL, Schenkel JM, Jaeger AM, Bronson RT, Westcott PMK, Hether TD, Divakar P, Reeves JW, Deshpande V, Delorey T, Phillips D, Yilmaz OH, Regev A, Jacks T. The CD155/TIGIT axis promotes and maintains immune evasion in neoantigen-expressing pancreatic cancer. Cancer Cell. 2021 Oct.39(10):1342-1360.e14. Pubmedid: 34358448. Pmcid: PMC8511341.
  • Raghavan S, Winter PS, Navia AW, Williams HL, DenAdel A, Lowder KE, Galvez-Reyes J, Kalekar RL, Mulugeta N, Kapner KS, Raghavan MS, Borah AA, Liu N, Väyrynen SA, Costa AD, Ng RWS, Wang J, Hill EK, Ragon DY, Brais LK, Jaeger AM, Spurr LF, Li YY, Cherniack AD, Booker MA, Cohen EF, Tolstorukov MY, Wakiro I, Rotem A, Johnson BE, McFarland JM, Sicinska ET, Jacks TE, Sullivan RJ, Shapiro GI, Clancy TE, Perez K, Rubinson DA, Ng K, Cleary JM, Crawford L, Manalis SR, Nowak JA, Wolpin BM, Hahn WC, Aguirre AJ, Shalek AK. Microenvironment drives cell state, plasticity, and drug response in pancreatic cancer. Cell. 2021 Dec.184(25):6119-6137.e26. Pubmedid: 34890551. Pmcid: PMC8822455.
  • Genshaft AS, Ziegler CGK, Tzouanas CN, Mead BE, Jaeger AM, Navia AW, King RP, Mana MD, Huang S, Mitsialis V, Snapper SB, Yilmaz ÖH, Jacks T, Van Humbeck JF, Shalek AK. Live cell tagging tracking and isolation for spatial transcriptomics using photoactivatable cell dyes. Nat Commun. 2021 Aug.12(1):4995. Pubmedid: 34404785. Pmcid: PMC8371137.
  • Dong B, Jaeger AM, Hughes PF, Loiselle DR, Hauck JS, Fu Y, Haystead TA, Huang J, Thiele DJ. Targeting therapy-resistant prostate cancer via a direct inhibitor of the human heat shock transcription factor 1. Sci Transl Med. 2020 Dec.12(574). Pubmedid: 33328331.
  • Jaeger AM, Stopfer L, Lee S, Gaglia G, Sandel D, Santagata S, Lin NU, Trepel JB, White F, Jacks T, Lindquist S, Whitesell L. Rebalancing Protein Homeostasis Enhances Tumor Antigen Presentation. Clin Cancer Res. 2019 Nov.25(21):6392-6405. Pubmedid: 31213460. Pmcid: PMC6825536.
  • Dong B, Jaeger AM, Thiele DJ. Inhibiting Heat Shock Factor 1 in Cancer: A Unique Therapeutic Opportunity. Trends Pharmacol Sci. 2019 Dec.40(12):986-1005. Pubmedid: 31727393.
  • Gomez-Pastor R, Burchfiel ET, Neef DW, Jaeger AM, Cabiscol E, McKinstry SU, Doss A, Aballay A, Lo DC, Akimov SS, Ross CA, Eroglu C, Thiele DJ. Abnormal degradation of the neuronal stress-protective transcription factor HSF1 in Huntington's disease. Nat Commun. 2017 Feb.8:14405. Pubmedid: 28194040. Pmcid: PMC5316841.
  • Jaeger AM, Pemble CW, Sistonen L, Thiele DJ. Structures of HSF2 reveal mechanisms for differential regulation of human heat-shock factors. Nat Struct Mol Biol. 2016 Feb.23(2):147-154. Pubmedid: 26727490. Pmcid: PMC4973471.
  • Jaeger AM, Makley LN, Gestwicki JE, Thiele DJ. Genomic heat shock element sequences drive cooperative human heat shock factor 1 DNA binding and selectivity. J Biol Chem. 2014 Oct.289(44):30459-30469. Pubmedid: 25204655. Pmcid: PMC4215228.
  • Neef DW, Jaeger AM, Gomez-Pastor R, Willmund F, Frydman J, Thiele DJ. A direct regulatory interaction between chaperonin TRiC and stress-responsive transcription factor HSF1. Cell Rep. 2014 Nov.9(3):955-966. Pubmedid: 25437552. Pmcid: PMC4488849.
  • Howe MK, Bodoor K, Carlson DA, Hughes PF, Alwarawrah Y, Loiselle DR, Jaeger AM, Darr DB, Jordan JL, Hunter LM, Molzberger ET, Gobillot TA, Thiele DJ, Brodsky JL, Spector NL, Haystead TA. Identification of an allosteric small-molecule inhibitor selective for the inducible form of heat shock protein 70. Chem Biol. 2014 Dec.21(12):1648-1659. Pubmedid: 25500222. Pmcid: PMC4272656.
  • Neef DW, Jaeger AM, Thiele DJ. Genetic selection for constitutively trimerized human HSF1 mutants identifies a role for coiled-coil motifs in DNA binding. G3 (Bethesda). 2013 Aug.3(8):1315-1324. Pubmedid: 23733891. Pmcid: PMC3737171.
  • Groer CE, Schmid CL, Jaeger AM, Bohn LM. Agonist-directed interactions with specific beta-arrestins determine mu-opioid receptor trafficking, ubiquitination, and dephosphorylation. J Biol Chem. 2011 Sep.286(36):31731-31741. Pubmedid: 21757712. Pmcid: PMC3173119.
  • Neef DW, Jaeger AM, Thiele DJ. Heat shock transcription factor 1 as a therapeutic target in neurodegenerative diseases. Nat Rev Drug Discov. 2011 Dec.10(12):930-944. Pubmedid: 22129991. Pmcid: PMC3518299.

Grants

  • Title: Exploring the Impact of HSP90 Inhibition on Antigen Presentation and Anti-Tumor Immune Responses
    Sponsor: Nat Institutes of Health
    PI: Jaeger, A.