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Eastern Colorado GRECC Investigator

Wendy Kohrt, PhD, is the former Director of Eastern Colorado GRECC.

Title: EC GRECC Investigator; Distinguished Professor of Medicine in the Division of Geriatric Medicine

Personal StatementWendy M Kohrt, PhD, is the former acting Director of the Eastern Colorado Geriatric Research, Education, and Clinical Center (GRECC). She is a Distinguished Professor of

Medicine in the Division of Geriatric Medicine and the Nancy Anschutz Chair in Women’s Health Research at the University of Colorado Anschutz Medical Campus. She holds several leadership

positions including Director of Research for Geriatric Medicine, Associate Director of the Ludeman Family Center for Women’s Health Research, Director of the Energy Balance Assessment Core

for the Colorado Nutrition and Obesity Research Center (NORC), and Associate Director of the Colorado Clinical and Translational Sciences Institute (CCTSI). Her research is focused on the

metabolic actions of estrogens and novel factors that influence the musculoskeletal adaptations to exercise. She has received continuous funding from the NIH as a principal investigator

since 1991 and has more than 280 research publications. Dr. Kohrt is currently the PI of a VA Merit Review and two NIH Center grants, including a Specialized Center of Research Excellence

(SCORE) in Sex Difference co-sponsored by the National Institute on Aging and the Office of Research on Women’s Health. She serves as Chair of the Steering Committee and Executive Steering

Committee for the NIH Common Fund Molecular Transducers of Physical Activity Consortium (MoTrPAC).

Dr. Kohrt’s VA research is focused on the disruption of calcium homeostasis by exercise. Some athletes, such as cyclists, have bone mineral density levels that are below normal. Although it

is commonly believed that this is because they participate in weight-supported exercise (as opposed to weight-bearing), the Kohrt group documented that competitive cyclists lose BMD at an

accelerated rate of 1% to 2% per year. They postulate that the disruption of calcium homeostasis during exercise contributes to this loss. The working model postulates that serum calcium

declines during exercise, which leads to an increase in parathyroid hormone (PTH) and the stimulation of bone resorption to mobilize calcium from bone and prevent the serum calcium level

from declining to a harmful level. They demonstrated that these changes occur in young and older, trained and untrained, women and men, and that the provision of supplemental calcium before

and during exercise attenuates the disruptions in PTH and bone resorption. The current VA project is investigating whether this catabolic response of bone to exercise is diminished after

repeated exercise bouts (i.e., exercise training).

Mentoring ActivitiesSince 1991, I have mentored or co-mentored 39 PhD-trained and 24 MD-trained research fellows from several departments/divisions (Geriatric Medicine, General Internal

Medicine, Endocrinology, Infectious Diseases, Cardiology); the majority have established independent research careers. I serve as a senior faculty mentor on the following institutional

training grants: Integrative Physiology of Aging (T32 AG000279); Nutrition (T32 DK007658; Colorado Building Interdisciplinary Research Careers in Women’s Health (K12 HD057022); and Colorado

WHRH Career Development Center (K12 HD001271). I have served as mentor or co-mentor for 29 postdoctoral fellows supported by a T32 award, 8 supported by an F32 award, and 21 supported by a

VA CDA or NIH K award.

Physical activity is known to have many beneficial effects on health, but the mechanisms by which this occurs are not well understood.In 2016, the NIH Common Fund launched MoTrPAC to address

this knowledge gap. MoTrPAC consists of several components (Clinical Centers, Preclinical Animal Sites, Chemical Analysis Sites, Bioinformatics Center, Coordinating Center) that are working

together to develop a compendium of the molecular responses to acute exercise and exercise training, with a long-range goal of elucidating the mechanisms by which exercise improves

health.The final product of this initiative, which will be shared with the scientific community and the public, will be the MoTrPAC DataHub, populated with multi-omic, multi-tissue, and

multi-species molecular and phenotypic data characterizing responses to acute and chronic endurance and resistance exercise.Dr. Kohrt serves as the PI of the Colorado Clinical Center and as

the Chair of the MoTrPAC Steering Committee and Executive Steering Committee. Funder: National Institutes of HealthNIH websiteRecruiting ↠ Find out how to participate in the MoTrPAC study.

Exercise is essential for building and maintaining bone mass and strength. Still, current recommendations for achieving this need more detail on the optimal exercise prescription. Recent

studies found that blood calcium level decreases during exercise and that calcium is mobilized from bone to slow the decline. If this repeatedly occurs during exercise training, it could

diminish the potential benefits of exercise to improve bone health. The proposed studies will determine whether taking supplemental calcium before exercise to minimize the decline in blood

calcium levels is an effective way to improve the skeletal benefits of exercise. This research is essential for Veterans because they are at increased risk of hip fracture compared to

non-Veterans. Further, because osteoporosis in men is under-recognized and under-treated, providing male (and female) Veterans with more specific exercise and nutrition guidelines can

enhance bone health, reduce fracture risk, and improve quality of life.Funder: Veterans AffairsNIH websiteRecruiting ↠ The study Enhancing Skeletal Adaptations – PTH and Exercise (ESkAPE) is

recruiting research subjects, click to learn more.

Role: PIThe decline in sex hormones (estrogen and testosterone) with aging can increase the risk for certain diseases; osteoporosis is a well-known example. The loss of estrogen is

significant for women’s health because it occurs during mid-life. In contrast, the loss of testosterone in men occurs much later in life. The Colorado Specialized Center of Research

Excellence on Sex Differences (CO-SCORE) will advance novel ideas for how the loss of estrogen increases fat gain in the abdominal region, which increases the risk for heart disease and

diabetes, and strategies that may be effective in preventing this.Funder: National Institute on AgingNIH websitePublications of note:— Oxidative Stress and Inflammation Are Associated With

Age-Related Endothelial Dysfunction in Men With Low Testosterone— Sex Differences in Peripheral Artery Disease— Body composition and cardiometabolic health across the menopause transition—

Metabolite G-Protein Coupled Receptors in Cardio-Metabolic Diseases

Role: Director of ResearchThe areas of women's health and sex differences research have long had an inadequate cadre of investigators with top-quality training sufficient to make them

competitive for limited research funding dollars. By using interdisciplinary training and excellent mentoring to develop the careers of the research leaders of tomorrow, we can address the

most important, pressing questions in women's health and sex and gender differences. By equipping early career scientists to find the answers, we expect this grant to lead the way to

tangible improvements in women's health in the United States.Funder: Eunice Kennedy Shriver National Institute of Child Health & Human DevelopmentNIH websitePublications of note:— Analysis

of Stroke Care Among 2019–2020 National Emergency Medical Services Information System Encounters— Obesity Management in Cardiometabolic Disease: State of the Art— Routine Screening for

Transgender and Gender Diverse Adults Taking Gender-Affirming Hormone Therapy: a Narrative Review— Sex differences in the burden of type 2 diabetes and cardiovascular risk across the life

course

Role: Mentor for PI: Sarah WherryThe decrease in serum ionized calcium and the increase in parathyroid hormone and c-telopeptide of type I collagen (a marker of bone formation) that occurs

during exercise, referred to as a disruption in calcium homeostasis, may explain why bone does not always result in the expected exercise-induced increase in bone mass or why exercise may

lead to bone loss under certain conditions. The disruption in calcium homeostasis has been well-characterized for acute endurance exercise. Still, the effects of resistance exercise and

training could be more precise. This study aims to determine if resistance exercise results in a different bone biomarker response than endurance exercise. The study also explores if ten

weeks of endurance or resistance training disrupts calcium homeostasis. Blood samples will be collected before, during, and after the exercise training period to assess changes in bone

resorption and formation markers. Data will be used to develop future exercise interventions in older Veterans to preserve bone health.Funder: Veterans AffairsNIH website

Beavers KM, Wolle BR, Ard JD, Beavers DP, Biehl O, Brubaker PH, Burghardt AJ, Calderone CT, Carballido-Gamio J, Fanning J, Kohrt WM, Love M, MacLean CM, Nicklas BJ, Stapleton J, Swanson CM,

Weaver AA, Worden M, Wherry SJ. The Bone, Exercise, Alendronate, and Caloric Restriction (BEACON) trial design and methods. Contemp Clin Trials. 2024 Sep 17;146:107692. doi:

10.1016/j.cct.2024.107692. Epub ahead of print. PMID: 39293778.

DuBose LE, Babcock MC, Kohrt WM, Stauffer BL, Hildreth KL, Walker J, Armstrong MK, Moreau KL. Gonadal status modulates large elastic artery stiffness in healthy middle-aged and older men.

Geroscience. 2024 Aug 7. doi: 10.1007/s11357-024-01293-y. Epub ahead of print. PMID: 39110324.

Kumar TR, Reusch JEB, Kohrt WM, Regensteiner JG; Conference Participants. Sex Differences Across the Lifespan: A Focus on Cardiometabolism. J Womens Health (Larchmt). 2024 Jul 26. doi:

10.1089/jwh.2024.0595. Epub ahead of print. PMID: 39056116.

Amar D, Gay NR, Jimenez-Morales D, Jean Beltran PM, Ramaker ME, Raja AN, Zhao B, Sun Y, Marwaha S, Gaul DA, Hershman SG, Ferrasse A, Xia A, Lanza I, Fernández FM, Montgomery SB, Hevener AL,

Ashley EA, Walsh MJ, Sparks LM, Burant CF, Rector RS, Thyfault J, Wheeler MT, Goodpaster BH, Coen PM, Schenk S, Bodine SC, Lindholm ME; MoTrPAC Study Group. The mitochondrial multi-omic

response to exercise training across rat tissues. Cell Metab. 2024 Jun 4;36(6):1411-1429.e10. doi: 10.1016/j.cmet.2023.12.021. Epub 2024 May 2. PMCID: PMC11152996.PMID: 38701776.

MoTrPAC Study Group; Lead Analysts; MoTrPAC Study Group. Temporal dynamics of the multi-omic response to endurance exercise training. Nature. 2024 May;629(8010):174-183. doi:

10.1038/s41586-023-06877-w. Epub 2024 May 1. PMCID: PMC11062907.PMID: 38693412.

Group MR, Jakicic JM, Kohrt WM, Houmard JA, Miller ME, Radom-Aizik S, Rasmussen BB, Ravussin E, Serra M, Stowe CL, Trappe S, AbouAssi H, Adkins JN, Alekel DL, Ashley E, Bamman MM, Bergman

BC, Bessesen DH, Broskey NT, Buford TW, Burant CF, Chen H, Christle JW, Clish CB, Coen PM, Collier D, Collins KA, Cooper DM, Cortes T, Cutter GR, Dubis G, Fernandez FM, Firnhaber J, Forman

DE, Gaul DA, Gay N, Gerszten RE, Goodpaster BH, Gritsenko MA, Haddad F, Huffman KM, Ilkayeva O, Jankowski CM, Jin C, Johannsen NM, Johnson J, Kelly L, Kershaw E, Kraus WE, Laughlin M, Lester

B, Lindholm ME, Lowe A, Lu CJ, McGowan J, Melanson EL, Montgomery S, Moore SG, Moreau KL, Muehlbauer M, Musi N, Nair VD, Newgard CB, Newman AB, Nicklas B, Nindle BC, Ormond K, Piehowski PD,

Qian WJ, Rankinen T, Rejeski WJ, Robbins J, Rogers RJ, Rooney JL, Rushing S, Sanford JA, Schauer IE, Schwartz RS, Sealfon SC, Slentz C, Sloan R, Smith KS, Snyder M, Spahn J, Sparks LM,

Stefanovic-Racic M, Tanner CJ, Thalacker-Mercer A, Tracy R, Trappe TA, Volpi E, Walsh MJ, Wheeler MT, Willis LH. Molecular Transducers of Physical Activity Consortium (MoTrPAC): Human

Studies Design and Protocol. J Appl Physiol (1985). 2024 Apr 18. doi: 10.1152/japplphysiol.00102.2024. Epub ahead of print. PMID: 38634503.

Libby AE, Solt C, Jackman M, Sherk V, Foright RM, Johnson GC, Nguyen TT, Breit M, Hulett N, Rudolph M, Roberson PA, Wellberg E, Jambal P, Scalzo RL, Higgins J, Kumar TR, Wierman ME, Pan Z,

Shankar K, Klemm DJ, Moreau KL, Kohrt WM, MacLean PS. Effects of Follicle Stimulating Hormone on Energy Balance and Tissue Metabolic Health After Loss of Ovarian Function. Am J Physiol

Endocrinol Metab. 2024 Mar 27. doi: 10.1152/ajpendo.00400.2023. Epub ahead of print. PMID: 38536037.

Blondin DP, Haman F, Swibas TM, Hogan-Lamarre S, Dumont L, Guertin J, Richard G, Weissenburger Q, Hildreth KL, Schauer IE, Panter S, Wayland L, Carpentier AC, Miao Y, Shi J, Juarez-Colunga

E, Kohrt WM, Melanson EL. Brown Adipose Tissue Metabolism in Women is Dependent on Ovarian Status. Am J Physiol Endocrinol Metab. 2024 Mar 13. doi: 10.1152/ajpendo.00077.2024. Epub ahead of

print. PMID: 38477875.

Griffith G, Lamotte G, Mehta N, Fan P, Nikolich J, Springman V, Suttman E, Joslin E, Balfany K, Dunlap M, Kohrt WM, Christiansen CL, Melanson EL, Josbeno D, Chahine LM, Patterson CG, Corcos

DM. Chronotropic Incompetence During Exercise Testing as a Marker of Autonomic Dysfunction in Individuals with Early Parkinson's Disease. J Parkinsons Dis. 2024 Jan 4. doi:

10.3233/JPD-230006. Epub ahead of print. PMID: 38189712.

Shah VN, Qui S, Stoneback J, Qamar L, Ferguson VL, Kohrt WM, Snell-Bergeon JK, Rao SD. Bone Structure and Turnover in Postmenopausal Women With Long-Standing Type 1 Diabetes. JBMR Plus. 2023

Oct 15;7(11):e10831. doi: 10.1002/jbm4.10831. PMCID: PMC10652172. PMID: 38025041.

Buchanan C, Buchanan C, Riordan M, Byrd J, Schulte M, Kohrt WM, Ambardekar AV, Allen LA, Wolfel G, Lawley J, Levine BD, Cornwell WK 3rd. Cardiopulmonary Performance Among Heart Failure

Patients Before and After Left Ventricular Assist Device Implantation. JACC Heart Fail. 2023 Aug 7:S2213-1779(23)00367-0. doi: 10.1016/j.jchf.2023.06.017. Epub ahead of print. PMID:

37632493.

Patterson CG, Joslin E, Gil AB, Spigle W, Nemet T, Chahine L, Christiansen CL, Melanson E, Kohrt WM, Mancini M, Josbeno D, Balfany K, Griffith G, Dunlap MK, Lamotte G, Suttman E, Larson D,

Branson C, McKee KE, Goelz L, Poon C, Tilley B, Kang UJ, Tansey MG, Luthra N, Tanner CM, Haus JM, Fantuzzi G, McFarland NR, Gonzalez-Latapi P, Foroud T, Motl R, Schwarzschild MA, Simuni T,

Marek K, Naito A, Lungu C, Corcos DM; SPARX3-PSG Investigators. Study in Parkinson's disease of exercise phase 3 (SPARX3): study protocol for a randomized controlled trial. Trials. 2022 Oct

6;23(1):855. doi: 10.1186/s13063-022-06703-0. PMCID: PMC9535216. PMID: 36203214.

Dolan E, Dumas A, Keane KM, Bestetti G, Freitas LHM, Gualano B, Kohrt WM, Kelley GA, Pereira RMR, Sale C, Swinton PA. The Bone Biomarker Response to an Acute Bout of Exercise: A Systematic

Review with Meta-Analysis. Sports Med. 2022 Jul 23. doi: 10.1007/s40279-022-01718-8. Epub ahead of print. PMID: 35870108.

Babcock MC, DuBose LE, Hildreth KL, Stauffer BL, Cornwell WK 3rd, Kohrt WM, Moreau KL. Age-associated reductions in cardiovagal baroreflex sensitivity are exaggerated in middle-aged and

older men with low testosterone. J Appl Physiol (1985). 2022 Jun 30. doi: 10.1152/japplphysiol.00245.2022. Epub ahead of print. PMID: 35771224.

Gavin KM, Sullivan TM, Maltzahn JK, Jackman MR, Libby AE, MacLean PS, Kohrt WM, Majka SM, Klemm DJ. Hematopoietic Stem Cell-Derived Adipocytes Modulate Adipose Tissue Cellularity, Leptin

Production and Insulin Responsiveness in Female Mice. Front Endocrinol (Lausanne). 2022 Jun 3;13:844877. doi: 10.3389/fendo.2022.844877. PMCID: PMC9203959. PMID: 35721743.

Swanson CM, Shanbhag P, Tussey EJ, Rynders CA, Wright KP Jr, Kohrt WM. Bone Turnover Markers After Six Nights of Insufficient Sleep and Subsequent Recovery Sleep in Healthy Men. Calcif

Tissue Int. 2022 Feb 8. doi: 10.1007/s00223-022-00950-8. Epub ahead of print. PMID: 35133471.

Marlatt KL, Pitynski-Miller DR, Gavin KM, Moreau KL, Melanson EL, Santoro N, Kohrt WM. Body composition and cardiometabolic health across the menopause transition. Obesity (Silver Spring).

2022 Jan;30(1):14-27. doi: 10.1002/oby.23289. PMID: 34932890.