Katherine Motyl, PhD

Faculty Scientist I


BA: Chemistry & Biology, Kalamzoo College
PhD: Physiology, Michigan State University

Motyl Lab 

Furthering our understanding of the brain-bone-metabolism connection.

Bone remodeling is an important process required for skeletal acclimation to the demands of weight bearing, for repairing bone fractures and micro cracks, and for maintaining blood calcium homeostasis. Bone remodeling is regulated by both local and systemic factors, including hormones and energy balance. Advancements in the field in the last 20 years have demonstrated that bone is also regulated by the nervous system.

My laboratory uses pharmacologic, genetic and disease models in order to further our understanding of the brain-bone-metabolism connection. We are particularly interested in the role of neuropathy in the pathogenesis of bone loss from type 1 diabetes. Another project is examining how the metabolic consequences of antipsychotic drugs relate to changes in bone remodeling (featured in video below). Finally, we are using genetic models to understand how temperature regulation is important for bone growth and maintenance. Understanding these pathways will give us insight into future therapeutics for bone diseases like osteoporosis.

To learn more about these and other projects in the Motyl lab, please see our publications or contact me directly at motylk@mmc.org. You can also follow us on Twitter at @MotylLab.

Motyl Lab Members


Adriana Carvalho

Research Fellow

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.

Audrey Bergeron

Research Associate I

It is well-known that elevated sympathetic nervous system (SNS) activity (also known as the “fight-or-flight” response) reduces bone formation and increases resorption, resulting in bone loss. Therefore, elevated SNS activity via the action of β-adrenergic receptor (βAR) signaling has been implicated in pathologies such as osteoporosis. βAR antagonists (β-blockers) provide a potential target for preventing and/or treating osteoporosis. My work focuses on characterizing the direct effects of βAR activity in bone-resorbing osteoclasts to determine potential mechanisms by which βAR stimulation affects intracellular signaling and osteoclast differentiation, activity, and function.

Audrie Langlais

Research Assistant II

Kathleen Nevola

Graduate Student
Kathleen.Nevola@tuft.edu, LinkedIn

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.

A complete list of publications can be found on My NCBI

Original Manuscripts:

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.

Review Publications

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.

Academic Appointments

  • Faculty Scientist I, Maine Medical Center Research Institute, Scarborough, ME
  • Graduate Faculty, Graduate School of Biomedical Sciences and Engineering, University of Maine, Orono, ME
  • Assistant Professor, Department of Medicine, Tufts University School of Medicine, Boston, MA.

Professional Activities

  • Member, Editorial Board, Endocrinology
  • Member, American Association for the Advancement of Science
  • Member, American Society for Bone and Mineral Research
  • Member, The Endocrine Society
  • Member, Society for Neuroscience

The Motyl Lab Science Sketch video below demonstrates how the metabolic consequences of antipsychotic drugs relate to changes in bone remodeling.