Jason Doles, PhD
Associate Professor of Anatomy, Cell Biology & Physiology
Vice Chair for Strategic Engagement
- Address
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MS 310
ANAT
IN
Indianapolis, IN - PubMed:
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Bio
Dr. Jason Doles is an Associate Professor of Anatomy, Cell Biology, and Physiology where he leads a research group that studies skeletal muscle wasting, stem cells/tissue regeneration, and neuromuscular disease. In addition to research, Dr. Doles is a committed mentor, educator, and advocate for inclusion, belonging and well-being in the learning/research environment and beyond.
Learn more about the Doles lab here!
Professional highlights
- Vice Chair for Strategic Engagement, Department of Anatomy, Cell Biology and Physiology, IU School of Medicine; 2022-present
- Co-Director/Co-Founder, Leadership in PhD (LeaP) Program (Mayo Clinic); 2021-2022
- Assistant Dean of Diversity and Inclusion, Mayo Clinic Graduate School; 2020-2022
- Associate Program Director, Mayo Clinic Graduate School; 2020-2022
- Co-Leader, Mayo Clinic Post-Baccalaureate Research Education Program (PREP); 2016-2022
- Co-Leader, Mayo Clinic Initiative for Maximizing Student Development (IMSD); 2016-2022
LinkedIn: https://www.linkedin.com/in/jason-doles
Twitter: https://twitter.com/jdoles99
Key Publications
Primary research
Dasgupta A, Gibbard DF, Schmitt RE, Arneson-Wissink PC, Ducharme AM, Bruinsma ES, Hawse JR, Jatoi A, Doles JD. (2023) A TGF-β/KLF10 signaling axis regulates atrophy-associated genes to induce muscle wasting in pancreatic cancer. Proc Natl Acad Sci U S A. Aug 22;120(34):e2215095120.
Neyroud D, Laitano O, Dasgupta A, Lopez C, Schmitt RE, Schneider JZ, Hammers DW, Sweeney HL, Walter GA, Doles J, Judge SM, Judge AR. Blocking muscle wasting via deletion of the muscle-specific E3 ligase MuRF1 impedes pancreatic tumor growth. Commun Biol. 2023 May 13;6(1):519.
Schmitt RE, Dasgupta A, Arneson-Wissink PC, Datta S, Ducharme AM, Doles JD. Muscle stem cells contribute to long-term tissue repletion following surgical sepsis. J Cachexia Sarcopenia Muscle. (2023) Jun;14(3):1424-1440.
Nicolau S, Dasgupta A, Dasari S, Charlesworth MC, Johnson KL, Pandey A, Doles JD, Milone M. Molecular signatures of inherited and acquired sporadic late onset nemaline myopathies. Acta Neuropathol Commun. 2023 Jan 26;11(1):20.
Hogenson TL, Xie H, Phillips WJ, Toruner MD, Li JJ, Horn IP, Kennedy DJ, Almada LL, Marks DL, Carr RM, Toruner M, Sigafoos AN, Koenig-Kappes AN, Olson RL, Tolosa EJ, Zhang C, Li H, Doles JD, Bleeker J, Barrett MT, Boyum JH, Kipp BR, Mahipal A, Hubbard JM, Scheffler Hanson TJ, Petersen GM, Dasari S, Oberg AL, Truty MJ, Graham RP, Levy MJ, Zhu M, Billadeau DD, Adjei AA, Dusetti N, Iovanna JL, Bekaii-Saab TS, Ma WW, Fernandez-Zapico ME. Culture media composition influences patient-derived organoid ability to predict therapeutic responses in gastrointestinal cancers. JCI Insight. 2022 Nov 22;7(22):e158060.
Schmitt RE, Smith DY 4th, Cho DS, Kirkeby LA, Resch ZT, Liewluck T, Niu Z, Milone M, Doles JD. Myogenesis defects in a patient-derived iPSC model of hereditary GNE myopathy. NPJ Regen Med. 2022 Sep 9;7(1):48.
Cho DS, Schmitt RE, Dasgupta A, Ducharme AM, Doles JD. Acute and sustained alterations to the bone marrow immune microenvironment following polymicrobial infection. Shock. 2022 Jul 1;58(1):45-55.
Dasgupta A, Arneson-Wissink PC, Schmitt RE, Cho DS, Ducharme AM, Hogenson TL, Krueger EW, Bamlet WR, Zhang L, Razidlo GL, Fernandez-Zapico ME, Doles JD. Anti-cachectic regulator analysis reveals novel Perp-dependent anti-tumorigenic properties of 3-methyladenine in pancreatic cancer. JCI Insight. 2021 Dec 7:e153842.
Arneson-Wissink PC, Doles JD. Disrupted NOS2 metabolism drives myoblast response to wasting-associated cytokines. Exp Cell Res. 2021 Oct 1;407(1):112779.
Cho DS, Schmitt RE, Dasgupta A, Ducharme AM, Doles JD. Single cell deconstruction of post-sepsis skeletal muscle and adipose tissue microenvironments. Journal of Cachexia, Sarcopenia and Muscle 2020 Jul 8.
Arneson PC, Hogan KA, Shin AS, Samani A, Jatoi A, Doles JD. The wasting-associated metabolite succinate disrupts myogenesis and impairs muscle regeneration. JCSM Rapid Communications. 2020 Jun 2.
Arneson PC, Dusharme AM, Doles JD. A novel transplantable model of lung cancer associated tissue loss and disrupted muscle regeneration. Skeletal Muscle. 2020 Mar 9;10(1):6.
Cho DS, Lee B, Doles JD. Refining the adipose progenitor cell landscape in healthy and obese visceral adipose tissue. Life Sci Alliance. 2019. Nov 25;2(6). pii. e201900561.
Joseph J, Cho DS, Doles JD. Metabolomic Analyses Reveal Extensive Progenitor Cell Deficiencies in a Mouse Model of Duchenne Muscular Dystrophy (2018). Metabolites. Oct 3;8(4). pii: E61.
Doles JD, Hogan KA, O'Connor J, Wahner Hendrickson AE, Huston O, Jatoi A. Does the Poly (ADP- Ribose) Polymerase Inhibitor Veliparib Merit Further Study for Cancer-Associated Weight Loss? Observations and Conclusions from Sixty Prospectively Treated Patients (2018). J Palliat Med. Sep;21(9):1334-1338.
Tarrago MG, Chini CCS, Kanamori KS, Warner GM, Caride A, de Oliveira GC, Rud M, Samani A, Hein KZ, Huang R, Jurk D, Cho DS, Boslett JJ, Miller JD, Zweier JL, Passos JF, Doles JD, Becherer DJ, Chini EN. A potent and specific CD38 inhibitor ameliorates age-related metabolic dysfunction by reversing tissue NAD+ decline (2018). Cell Metab. May 1;27(5):1081-1095.e10.
Hogan KA, Cho DS, Arneson P, Samani A, Palines P, Yang Y, Doles JD. Tumor- derived cytokines impair myogenesis and alter the skeletal muscle immune microenvironment (2017). Cytokine. Nov 16. pii: S1043-4666(17)30348-4.
Cho DS, Doles JD. Single cell transcriptome analysis of muscle satellite cells reveals widespread transcriptional heterogeneity (2017). Gene. Sep 8. pii: S0378-1119(17)30723-0.
Reviews/commentaries
Joseph J, Doles JD. Disease-associated metabolic alterations that impact satellite cells and muscle regeneration: perspectives and therapeutic outlook. Nutr Metab (Lond). 2021 Mar 25;18(1):33.
Arneson PC, Doles JD. Impaired Muscle Regeneration in Cancer-Associated Cachexia. Trends Cancer. 2019 Oct;5(10):579-582.
Cho DS, Doles JD. Skeletal Muscle Progenitor Cell Heterogeneity. Adv Exp Med Biol. 2019 Aug;1169:179-193.
Carr RM, Enriquez-Hesles E, Olson RL, Jatoi A, Doles J, Fernandez-Zapico ME. Epigenetics of cancer- associated muscle catabolism (2017). Epigenomics. Sep 25.
STEM education/career development
Doles MD, Kang JY, Scholl LM, Doles JD. Leadership in PhD (LeaP): a longitudinal leadership skill building program for underrepresented biomedical research trainees. Front. Educ. 8:1063075.
Boehmer KR, Boschen De Souza SL, Doles JD, Lachman N, Mays D, Hedin KE, Dornink CA, Maher LJ and Lujan J (2021) Motivating Self-Efficacy in Diverse Biomedical Science Postbaccalaureate and Graduate Students Through Scientific Conference Implementation. Front. Educ. 6:774070.
| Year | Degree | Institution |
|---|---|---|
| 2010 | PhD | Massachusetts Institute of Technology |
| 2003 | BA | Brown University |
Skeletal muscle regeneration
Satellite cells (SCs) are skeletal muscle resident adult stem cells required for muscle repair and regeneration. In uninjured muscle, SCs typically exist in a quiescent state until called upon to participate in tissue maintenance or repair. Upon exiting quiescence, SCs undergo substantial changes in gene expression, protein homeostasis and metabolic regulation.
Research in the lab investigates myogenic cell state transitions, with a focus on metabolic changes accompanying SC activation. Ongoing projects include single-cell gene expression studies, metabolic profiling of differentiating SCs, and examination of SC defects in the context of metabolic disorders. We are also interested in how SCs interact with the muscle microenvironment following traumatic tissue loss (i.e. volumetric muscle loss or ICU/sepsis-associated wasting).
Cancer cachexia
Cancer cachexia is a wasting disease associated with a decline in skeletal muscle mass and function. Approximately 60% to 80% of people with advanced cancer exhibit this comorbidity that is linked to increased mortality, disease morbidity, chemotherapeutic and surgical outcome, and quality of life. We study how tumors disrupt organismal homeostasis to promote muscle wasting.
Ongoing projects include studies to identify: 1) tumor-derived cytokines and metabolites, 2) immune cell contributions to regeneration defects, 3) the muscle stem cell response to wasting factors, and 4) novel targets/interventions to counteract lean mass loss.
Neuromuscular disease
Neuromuscular diseases (NMDs) collectively affect ~1/1,000 people and patients who suffer from these diseases typically sustain detrimental health effects that negatively impact quality of life and/or shorten lifespan. To date, most NMDs do not have cures or dependable treatments. This is partly due to significant gaps in knowledge regarding mechanisms influencing NMD onset and progression. Long term goals include the development and utilization of cell and animal models to study NMDs, identification of novel therapeutic targets, and testing of these targets in physiologically relevant pre-clinical settings.
Ongoing projects in the lab include: 1) use of patient-derived induced pluripotent stem cells to model GNE myopathy, 2) cell and tissue cross-talk in Duchenne Muscular Dystrophy (DMD), 3) regenerative therapy testing in GNE myopathy and DMD.