Motyl Lab Members
Research Assistant II
Research Assistant II
My postdoctoral research is focused on Trpm8 (transient receptor potential melastatin 8) a cold-sensing channel expressed by pain- and temperature-sensing neurons and its role in bone homeostasis. Previously, my PhD thesis was focused on bone and fat interaction in Type 1 Diabetes humans and streptozotocin mouse model and my Master dissertation was focused on the relationship between bone metabolism and dietary intake of women during menopausal transition.
During my research internship in the Motyl lab, I will be working on exploring sympathetic nervous regulation of bone remodelling. The focus of my experiments will primarily be on the metabolic effects of several atypical antipsychotic drugs in combination with temperature regulation in mouse models.
Risperidone is an atypical antipsychotic (AA) drug that is used to treat schizophrenia and bipolar disorder as well as complications of dementia in older adults. Previous research has shown an association between AA treatment and fractures and falls in clinical studies, and mouse studies have shown that risperidone treatment induces bone loss. Interestingly, co-therapy with the beta-blocker propranolol significantly curtailed bone loss, suggesting bone loss is due to metabolic consequences of sympathetic nervous system activation. My research goal is to develop a mechanistic understanding of this process by collecting and analyzing multi-omics data including mRNA, proteomic, and lipidomic data to investigate the mechanism through which sympathetic activation leads to bone loss in risperidone-treated mice. Furthermore, I will develop a robust pipeline and new methods for integration of multi-omic data sources that may be applied to other datasets.
Motyl KJ, Beauchemin M, Barlow D, Le PT, Nagano K, Treyball A, Contractor A, Baron R, Rosen CJ, Houseknecht KL. A novel role for dopamine signaling in the pathogenesis of bone loss from the atypical antipsychotic drug risperidone in female mice. Bone. 2017; 103:168-176. PMID: 28689816
Carvalho AL, DeMambro VE, Guntur AR, Le P, Nagano K, Baron R, de Paula FJA, Motyl KJ. High fat diet attenuates hyperglycemia, body composition changes, and bone loss in male streptozotocin-induced type 1 diabetic mice. Journal of Cellular Physiology. 2017; PMID: 28631813
Irwin R, Lin HV, Motyl KJ, McCabe LR. Normal bone density obtained in the absence of insulin receptor expression in bone. Endocrinology. 147(12):5760-5767, 2006. Highlighted in Endocrine News
Motyl KJ and LR McCabe. Leptin treatment prevents type I diabetic marrow adiposity but not bone loss in mice. J Cell Physiol. 218(2): 376-384, 2009. Highlighted in Science Now http://news.sciencemag.org/sciencenow/2010/03/appetite-suppressor-could-be-an-.html
Motyl KJ*, S Botolin*, R Irwin*, T Kadakia, A Amalfitano, RC Schwartz, and LR McCabe. Bone inflammation and altered gene expression with type I diabetes early onset. J Cell Physiol. 218(3):575-583. *authors contributed equally
Motyl KJ, and LR McCabe. Streptozotocin, type I diabetes severity and bone. Biological Procedures Online. Published online: 06 March 2009.
Motyl KJ, Raetz M, Tekalur SA, Schwartz RC, McCabe LR. CCAAT/enhancer binding protein beta-deficiency enhances type 1 diabetic bone phenotype by increasing marrow adiposity and bone resorption. Am J Physiol Regul Integr Comp Physiol. 2011;300(5):R1250-60.
Motyl KJ, McCauley LK, McCabe LR. Amelioration of Type I Diabetes-induced Osteoporosis by Parathyroid Hormone is Associated with Improved Osteoblast Survival. J Cell Physiol. 2012 Apr;227(4):1326-34.
Motyl KJ*, Dick-de-Paula I*, Maloney AE, Lotinun S, Bornstein S, de Paula FJ, Baron R, Houseknecht KL, Rosen CJ. Trabecular bone loss after administration of the second-generation antipsychotic risperidone is independent of weight gain. Bone. 2012;Feb;50(2):490-8. *authors contributed equally
Motyl KJ, Bishop KA, Demambro VE, Bornstein SA, Le P, Kawai M, Lotinun S, Horowitz MC, Baron R, Bouxsein ML, Rosen CJ. Altered thermogenesis and impaired bone remodeling in Misty mice. J Bone Miner Res. 2013. 28(9):1885-97. PMCID: PMC3743939.
Devlin MJ, Van Vliet M, Motyl K, Karim L, Brooks DJ, Louis L, Conlon C, Rosen CJ, Bouxsein ML. Early-onset type 2 diabetes impairs skeletal acquisition in the male TALLYHO/JngJ mouse. Endocrinology. 2014. Oct;155(10):3806-16. PMCID: PMC4164927.
Motyl KJ, DeMambro VE, Barlow D, Olshan D, Nagano K, Baron R, Rosen CJ, Houseknecht, CJ. Propranolol attenuates trabecular bone loss in female mice from the atypical antipsychotic, risperidone. Endocrinology. 2015; 156(7):2374-83. PMID: 25853667. **highlighted in Endocrine News.
Zhang J, Motyl KJ, Irwin R, MacDougald OA, Britton RA and McCabe LR. Loss of bone and Wnt10b expression with type 1 diabetes is blocked by the probiotic L. reuteri. Endocrinology. 2015; 156(9):3169-82.
Rosen CJ, Motyl KJ. No bones about it: insulin modulates skeletal remodeling. Cell. 2010;142(2):198-200.
Motyl KJ, McCabe LR, Schwartz AV. Bone and glucose metabolism: A two-way street. Arch Biochem Biophys. 2010 Nov 1;503(1):2-10.
Motyl KJ, Rosen CJ. Temperatures rising: Brown fat and bone. Discov Med. 2011 Mar;11(58):179-85.
Motyl KJ, Rosen CJ. Understanding leptin-dependent regulation of skeletal homeostasis. Biochimie. 2012 Oct;94(10):2089-96.
Motyl KJ, Rosen CJ. The skeleton and the sympathetic nervous system: it’s about time! J Clin Endocrinol Metab. 2012 Nov;97(11):3908-11.
Calarge CA, Ivins SD, Motyl KJ, Shibli-Rahhal AA, Bliziotes MM, and Schlechte JA. Possible mechanisms for the skeletal effects of antipsychotics in children and adolescents. Therapeutic Advances in Psychopharmacology. 3(5): 278-93. 2013. PMCID: PMC3805387.