Andrea Bonetto, PhD

Professional Titles

• Associate Professor of Pathology

Recognitions

• Research Scholar, American Cancer Society (2018)
• Research Scholar, The V Foundation for Cancer Research (2017)
• Research Scholar, Showalter Research Trust (2018)
• Excellence in Research - Next Generation Cancer Cachexia Researcher, Cancer Cachexia Society (2018)

Research Interests

I completed my MSc in Industrial Biotechnology and my PhD in Experimental Pathology at University of Torino, Italy, investigating the causes responsible for the development of cachexia, a severe complication of cancer, responsible for up to 30% of all cancer deaths. During my postdoctoral training at University of Miami and Thomas Jefferson University, I worked on unraveling the mechanisms of muscle wasting in the occurrence of cancer, with particular focus on the role of the pro-inflammatory IL-6/STAT3 signaling pathway. After joining Indiana University for my first faculty appointment, I contributed to develop new models for the study of cachexia in ovarian and colorectal cancer. My main research interest was focused on understanding the effects of chemotherapy in muscle and bone, as well as on the whole-body energy metabolism, with the goal of identifying therapeutic strategies aimed at reducing the side toxicity of anticancer treatments. Currently, I am an Associate Professor in the Department of Pathology at University of Colorado Anschutz Medical Campus and am interested in investigating the liver-bone-muscle interactions in colorectal cancer. Indeed, we have identified factors secreted by the liver that play a critical role in causing muscle and bone dysfunctions in subjects affected with colorectal cancer. Since 2006, I have authored over 60 publications and more than 100 communications/presentations to national and international meetings. My laboratory has been continuously funded by grants from V Foundation for Cancer Research, American Cancer Society and NIH/NIAMS.

Publications

• Huot JR, Pin F, Chatterjee R, Bonetto A. PGC1a overexpression preserves muscle mass and function in cisplatin-induced cachexia. J Cachexia Sarcopenia Muscle. 2022 Oct;13(5):2480-2491. PubMed PMID: 35903870
• Pin F, Jones AJ, Huot JR, Narasimhan A, Zimmers TA, Bonewald LF, Bonetto A. RANKL Blockade Reduces Cachexia and Bone Loss Induced by Non-Metastatic Ovarian Cancer in Mice. J Bone Miner Res. 2022 Mar;37(3):381-396. PubMed PMID: 34904285
• Jones AJ, Davis KP, Novinger LJ, Bonetto A, Mantravadi AV, Sim MW, Yesensky JA, Moore MG. Postoperative consequences of cancer cachexia after head and neck free flap reconstruction. Head Neck. 2022 Jul;44(7):1665-1677. PubMed PMID: 35488469
• Pin F, Huot JR, Bonetto A. The Mitochondria-Targeting Agent MitoQ Improves Muscle Atrophy, Weakness and Oxidative Metabolism in C26 Tumor-Bearing Mice. Front Cell Dev Biol. 2022;10:861622. PubMed PMID: 35392166
• Kim HG, Huot JR, Pin F, Belcher DJ, Bonetto A, Nader GA. Metastatic or xenograft colorectal cancer models induce divergent anabolic deficits and expression of pro-inflammatory effectors of muscle wasting in a tumor-type-dependent manner. J Appl Physiol (1985). 2022 Dec 1;133(6):1273-1283. PubMed PMID: 36201323
• Essex AL, Deosthale P, Huot JR, Davis HM, Momeni N, Bonetto A, Plotkin LI. miR21 deletion in osteocytes has direct and indirect effects on skeletal muscle in a sex-dimorphic manner in mice. Biol Sex Differ. 2022 Oct 1;13(1):56. PubMed PMID: 36183096
• Pin F, Bonewald LF, Bonetto A. Role of myokines and osteokines in cancer cachexia. Exp Biol Med (Maywood). 2021 Oct;246(19):2118-2127. PubMed PMID: 33899538
• Runco DV, Zimmers TA, Bonetto A. The urgent need to improve childhood cancer cachexia. Trends Cancer. 2022 Dec;8(12):976-979. PubMed PMID: 35931609
• Essex AL, Huot JR, Deosthale P, Wagner A, Figueras J, Davis A, Damrath J, Pin F, Wallace J, Bonetto A, Plotkin LI. Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) R47H Variant Causes Distinct Age- and Sex-Dependent Musculoskeletal Alterations in Mice. J Bone Miner Res. 2022 Jul;37(7):1366-1381. PubMed PMID: 35575023
• Pin F, Prideaux M, Huot JR, Essex AL, Plotkin LI, Bonetto A, Bonewald LF. Non-bone metastatic cancers promote osteocyte-induced bone destruction. Cancer Lett. 2021 Nov 1;520:80-90. PubMed PMID: 34233150
• Rupert JE, Narasimhan A, Jengelley DHA, Jiang Y, Liu J, Au E, Silverman LM, Sandusky G, Bonetto A, Cao S, Lu X, O'Connell TM, Liu Y, Koniaris LG, Zimmers TA. Tumor-derived IL-6 and trans-signaling among tumor, fat, and muscle mediate pancreatic cancer cachexia. J Exp Med. 2021 Jun 7;218(6). PubMed PMID: 33851955
• Jones AJ, Campiti VJ, Alwani M, Novinger LJ, Bonetto A, Sim MW, Yesensky JA, Moore MG, Mantravadi AV. Skeletal Muscle Index's Impact on Discharge Disposition After Head and Neck Cancer Free Flap Reconstruction. Otolaryngol Head Neck Surg. 2021 Jul;165(1):59-68. PubMed PMID: 33290190
• Kim HG, Huot JR, Pin F, Guo B, Bonetto A, Nader GA. Reduced rDNA transcription diminishes skeletal muscle ribosomal capacity and protein synthesis in cancer cachexia. FASEB J. 2021 Feb;35(2):e21335. PubMed PMID: 33527503
• Pin F, Prideaux M, Bonewald LF, Bonetto A. Osteocytes and Cancer. Curr Osteoporos Rep. 2021 Dec;19(6):616-625. PubMed PMID: 34773212
• Jones AJ, Campiti VJ, Alwani M, Novinger LJ, Tucker BJ, Bonetto A, Yesensky JA, Sim MW, Moore MG, Mantravadi AV. Sarcopenia is associated with blood transfusions in head and neck cancer free flap surgery. Laryngoscope Investig Otolaryngol. 2021 Apr;6(2):200-210. PubMed PMID: 33869752
• O'Connell TM, Golzarri-Arroyo L, Pin F, Barreto R, Dickinson SL, Couch ME, Bonetto A. Metabolic Biomarkers for the Early Detection of Cancer Cachexia. Front Cell Dev Biol. 2021;9:720096. PubMed PMID: 34621740
• Huot JR, Pin F, Bonetto A. Erratum: Muscle weakness caused by cancer and chemotherapy is associated with loss of motor unit connectivity. Am J Cancer Res. 2022;12(3):1435. PubMed PMID: 35411220
• Huot JR, Pin F, Bonetto A. Muscle weakness caused by cancer and chemotherapy is associated with loss of motor unit connectivity. Am J Cancer Res. 2021;11(6):2990-3001. PubMed PMID: 34249440
• Wang L, Halliday G, Huot JR, Satoh T, Baust JJ, Fisher A, Cook T, Hu J, Avolio T, Goncharov DA, Bai Y, Vanderpool RR, Considine RV, Bonetto A, Tan J, Bachman TN, Sebastiani A, McTiernan CF, Mora AL, Machado RF, Goncharova EA, Gladwin MT, Lai YC. Treatment With Treprostinil and Metformin Normalizes Hyperglycemia and Improves Cardiac Function in Pulmonary Hypertension Associated With Heart Failure With Preserved Ejection Fraction. Arterioscler Thromb Vasc Biol. 2020 Jun;40(6):1543-1558. PubMed PMID: 32268788
• Alwani MM, Jones AJ, Novinger LJ, Pittelkow E, Bonetto A, Sim MW, Moore MG, Mantravadi AV. Erratum: Impact of Sarcopenia on Outcomes of Autologous Head and Neck Free Tissue Reconstruction. J Reconstr Microsurg. 2020 Jun;36(5):e1. PubMed PMID: 32252095
• Alwani MM, Jones AJ, Novinger LJ, Pittelkow E, Bonetto A, Sim MW, Moore MG, Mantravadi AV. Impact of Sarcopenia on Outcomes of Autologous Head and Neck Free Tissue Reconstruction. J Reconstr Microsurg. 2020 Jun;36(5):369-378. PubMed PMID: 32088918
• Dolly A, Pötgens SA, Thibaut MM, Neyrinck AM, de Castro GS, Galbert C, Lefevre C, Wyart E, Gomes SP, Gonçalves DC, Lanthier N, Baldin P, Huot JR, Bonetto A, Seelaender M, Delzenne NM, Sokol H, Bindels LB. Impairment of aryl hydrocarbon receptor signalling promotes hepatic disorders in cancer cachexia. J Cachexia Sarcopenia Muscle. 2023 Jun;14(3):1569-1582. PubMed PMID: 37127348
• Huot JR, Pin F, Narasimhan A, Novinger LJ, Keith AS, Zimmers TA, Willis MS, Bonetto A. ACVR2B antagonism as a countermeasure to multi-organ perturbations in metastatic colorectal cancer cachexia. J Cachexia Sarcopenia Muscle. 2020 Dec;11(6):1779-1798. PubMed PMID: 33200567
• Huot JR, Baumfalk D, Resendiz A, Bonetto A, Smuder AJ, Penna F. Targeting Mitochondria and Oxidative Stress in Cancer- and Chemotherapy-Induced Muscle Wasting. Antioxid Redox Signal. 2023 Feb;38(4-6):352-370. PubMed PMID: 36310444
• Pin F, Novinger LJ, Huot JR, Harris RA, Couch ME, O'Connell TM, Bonetto A. PDK4 drives metabolic alterations and muscle atrophy in cancer cachexia. FASEB J. 2019 Jun;33(6):7778-7790. PubMed PMID: 30894018
• Davis HM, Essex AL, Valdez S, Deosthale PJ, Aref MW, Allen MR, Bonetto A, Plotkin LI. Short-term pharmacologic RAGE inhibition differentially affects bone and skeletal muscle in middle-aged mice. Bone. 2019 Jul;124:89-102. PubMed PMID: 31028960
• Pin F, Barreto R, Couch ME, Bonetto A, O'Connell TM. Cachexia induced by cancer and chemotherapy yield distinct perturbations to energy metabolism. J Cachexia Sarcopenia Muscle. 2019 Feb;10(1):140-154. PubMed PMID: 30680954
• Callaway CS, Mouchantat LM, Bitler BG, Bonetto A. Mechanisms of Ovarian Cancer-Associated Cachexia. Endocrinology. 2023 Nov 19. [Epub ahead of print] PubMed PMID: 37980602
• Essex AL, Pin F, Huot JR, Bonewald LF, Plotkin LI, Bonetto A. Bisphosphonate Treatment Ameliorates Chemotherapy-Induced Bone and Muscle Abnormalities in Young Mice. Front Endocrinol (Lausanne). 2019;10:809. PubMed PMID: 31803146
• Pin F, Bonetto A, Bonewald LF, Klein GL. Molecular Mechanisms Responsible for the Rescue Effects of Pamidronate on Muscle Atrophy in Pediatric Burn Patients. Front Endocrinol (Lausanne). 2019;10:543. PubMed PMID: 31447786
• Pin F, Couch ME, Bonetto A. Preservation of muscle mass as a strategy to reduce the toxic effects of cancer chemotherapy on body composition. Curr Opin Support Palliat Care. 2018 Dec;12(4):420-426. PubMed PMID: 30124526
• Pin F, Barreto R, Kitase Y, Mitra S, Erne CE, Novinger LJ, Zimmers TA, Couch ME, Bonewald LF, Bonetto A. Growth of ovarian cancer xenografts causes loss of muscle and bone mass: a new model for the study of cancer cachexia. J Cachexia Sarcopenia Muscle. 2018 Aug;9(4):685-700. PubMed PMID: 30009406
• Jones AJ, Novinger LJ, Bonetto A, Davis KP, Giuliano MM, Mantravadi AV, Sim MW, Moore MG, Yesensky JA. Histopathologic Features of Mucosal Head and Neck Cancer Cachexia. Int J Surg Oncol. 2024;2024:5339292. PubMed PMID: 38966634
• Huot JR, Livingston PD, Pin F, Thomas CR, Jamnick NA, Callaway CS, Bonetto A. Long-term Musculoskeletal Consequences of Chemotherapy in Pediatric Mice. Function (Oxf). 2024;5(3):zqae011. PubMed PMID: 38706958
• Balanta-Melo J, Jones AJ, Novinger LJ, Moore MG, Bonetto A. Masseter muscle thickness is predictive of cancer cachexia in patients with head and neck cancer. Head Neck. 2024 Nov;46(11):2678-2686. PubMed PMID: 38661244
• Mota R, Rodríguez JE, Bonetto A, O'Connell TM, Asher SA, Parry TL, Lockyer P, McCudden CR, Couch ME, Willis MS. Post-translationally modified muscle-specific ubiquitin ligases as circulating biomarkers in experimental cancer cachexia. Am J Cancer Res. 2017;7(9):1948-1958. PubMed PMID: 28979816
• Penna F, Bonetto A, Aversa Z, Minero VG, Rossi Fanelli F, Costelli P, Muscaritoli M. Effect of the specific proteasome inhibitor bortezomib on cancer-related muscle wasting. J Cachexia Sarcopenia Muscle. 2016 Jun;7(3):345-54. PubMed PMID: 27239411
• Zimmers TA, Fishel ML, Bonetto A. STAT3 in the systemic inflammation of cancer cachexia. Semin Cell Dev Biol. 2016 Jun;54:28-41. PubMed PMID: 26860754
• Barreto R, Waning DL, Gao H, Liu Y, Zimmers TA, Bonetto A. Chemotherapy-related cachexia is associated with mitochondrial depletion and the activation of ERK1/2 and p38 MAPKs. Oncotarget. 2016 Jul 12;7(28):43442-43460. PubMed PMID: 27259276
• Bonetto A, Kays JK, Parker VA, Matthews RR, Barreto R, Puppa MJ, Kang KS, Carson JA, Guise TA, Mohammad KS, Robling AG, Couch ME, Koniaris LG, Zimmers TA. Differential Bone Loss in Mouse Models of Colon Cancer Cachexia. Front Physiol. 2016;7:679. PubMed PMID: 28123369
• Barreto R, Mandili G, Witzmann FA, Novelli F, Zimmers TA, Bonetto A. Cancer and Chemotherapy Contribute to Muscle Loss by Activating Common Signaling Pathways. Front Physiol. 2016;7:472. PubMed PMID: 27807421
• Bonetto A, Andersson DC, Waning DL. Assessment of muscle mass and strength in mice. Bonekey Rep. 2015;4:732. PubMed PMID: 26331011
• Bonetto A, Penna F, Aversa Z, Mercantini P, Baccino FM, Costelli P, Ziparo V, Lucia S, Rossi Fanelli F, Muscaritoli M. Early changes of muscle insulin-like growth factor-1 and myostatin gene expression in gastric cancer patients. Muscle Nerve. 2013 Sep;48(3):387-92. PubMed PMID: 23861230
• Merli M, Giusto M, Molfino A, Bonetto A, Rossi M, Ginanni Corradini S, Baccino FM, Rossi Fanelli F, Costelli P, Muscaritoli M. MuRF-1 and p-GSK3ß expression in muscle atrophy of cirrhosis. Liver Int. 2013 May;33(5):714-21. PubMed PMID: 23432902
• Pedroso FE, Spalding PB, Cheung MC, Yang R, Gutierrez JC, Bonetto A, Zhan R, Chan HL, Namias N, Koniaris LG, Zimmers TA. Inflammation, organomegaly, and muscle wasting despite hyperphagia in a mouse model of burn cachexia. J Cachexia Sarcopenia Muscle. 2012 Sep;3(3):199-211. PubMed PMID: 22476919
• Bonetto A, Aydogdu T, Jin X, Zhang Z, Zhan R, Puzis L, Koniaris LG, Zimmers TA. JAK/STAT3 pathway inhibition blocks skeletal muscle wasting downstream of IL-6 and in experimental cancer cachexia. Am J Physiol Endocrinol Metab. 2012 Aug 1;303(3):E410-21. PubMed PMID: 22669242
• Aversa Z, Bonetto A, Penna F, Costelli P, Di Rienzo G, Lacitignola A, Baccino FM, Ziparo V, Mercantini P, Rossi Fanelli F, Muscaritoli M. Changes in myostatin signaling in non-weight-losing cancer patients. Ann Surg Oncol. 2012 Apr;19(4):1350-6. PubMed PMID: 21519918
• Aversa Z, Bonetto A, Costelli P, Minero VG, Penna F, Baccino FM, Lucia S, Rossi Fanelli F, Muscaritoli M. ß-hydroxy-ß-methylbutyrate (HMB) attenuates muscle and body weight loss in experimental cancer cachexia. Int J Oncol. 2011 Mar;38(3):713-20. PubMed PMID: 21184031
• Bonetto A, Penna F, Minero VG, Reffo P, Costamagna D, Bonelli G, Baccino FM, Costelli P. Glutamine prevents myostatin hyperexpression and protein hypercatabolism induced in C2C12 myotubes by tumor necrosis factor-a. Amino Acids. 2011 Feb;40(2):585-94. PubMed PMID: 20623149
• Bonetto A, Aydogdu T, Kunzevitzky N, Guttridge DC, Khuri S, Koniaris LG, Zimmers TA. STAT3 activation in skeletal muscle links muscle wasting and the acute phase response in cancer cachexia. PLoS One. 2011;6(7):e22538. PubMed PMID: 21799891
• Gazzerro E, Bonetto A, Minetti C. Caveolinopathies: translational implications of caveolin-3 in skeletal and cardiac muscle disorders. Handb Clin Neurol. 2011;101:135-42. PubMed PMID: 21496630
• Penna F, Bonetto A, Muscaritoli M, Costamagna D, Minero VG, Bonelli G, Rossi Fanelli F, Baccino FM, Costelli P. Muscle atrophy in experimental cancer cachexia: is the IGF-1 signaling pathway involved?. Int J Cancer. 2010 Oct 1;127(7):1706-17. PubMed PMID: 20039316
• Gazzerro E, Assereto S, Bonetto A, Sotgia F, Scarfì S, Pistorio A, Bonuccelli G, Cilli M, Bruno C, Zara F, Lisanti MP, Minetti C. Therapeutic potential of proteasome inhibition in Duchenne and Becker muscular dystrophies. Am J Pathol. 2010 Apr;176(4):1863-77. PubMed PMID: 20304949
• Bonetto A, Penna F, Muscaritoli M, Minero VG, Rossi Fanelli F, Baccino FM, Costelli P. Are antioxidants useful for treating skeletal muscle atrophy?. Free Radic Biol Med. 2009 Oct 1;47(7):906-16. PubMed PMID: 19591922
• Bonetto A, Penna F, Minero VG, Reffo P, Bonelli G, Baccino FM, Costelli P. Deacetylase inhibitors modulate the myostatin/follistatin axis without improving cachexia in tumor-bearing mice. Curr Cancer Drug Targets. 2009 Aug;9(5):608-16. PubMed PMID: 19508174
• Rossi S, Stoppani E, Martinet W, Bonetto A, Costelli P, Giuliani R, Colombo F, Preti A, Marchesini S, Fanzani A. The cytosolic sialidase Neu2 is degraded by autophagy during myoblast atrophy. Biochim Biophys Acta. 2009 Aug;1790(8):817-28. PubMed PMID: 19371771
• Costelli P, Muscaritoli M, Bonetto A, Penna F, Reffo P, Bossola M, Bonelli G, Doglietto GB, Baccino FM, Rossi Fanelli F. Muscle myostatin signalling is enhanced in experimental cancer cachexia. Eur J Clin Invest. 2008 Jul;38(7):531-8. PubMed PMID: 18578694
• Muscaritoli M, Costelli P, Aversa Z, Bonetto A, Baccino FM, Rossi Fanelli F. New strategies to overcome cancer cachexia: from molecular mechanisms to the 'Parallel Pathway'. Asia Pac J Clin Nutr. 2008;17 Suppl 1:387-90. PubMed PMID: 18296386
• Costelli P, Muscaritoli M, Bossola M, Penna F, Reffo P, Bonetto A, Busquets S, Bonelli G, Lopez-Soriano FJ, Doglietto GB, Argilés JM, Baccino FM, Rossi Fanelli F. IGF-1 is downregulated in experimental cancer cachexia. Am J Physiol Regul Integr Comp Physiol. 2006 Sep;291(3):R674-83. PubMed PMID: 16614058
• Mitra S, Tiwari K, Podicheti R, Pandhiri T, Rusch DB, Bonetto A, Zhang C, Mitra AK. Transcriptome Profiling Reveals Matrisome Alteration as a Key Feature of Ovarian Cancer Progression. Cancers (Basel). 2019 Oct 9;11(10). PubMed PMID: 31600962

Professional Memberships

• AACR, American Association for Cancer Research
• CCS, Cancer Cachexia Society
• SCWD, Society on Sarcopenia, Cachexia & Wasting Disorders
• APS, American Physiological Society
• ASBMR, American Society for Bone and Mineral Research