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Geriatric Research Education and Clinical Center (GRECC)

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Dwight Klemm PhD

 

Title: Principal Investigator; Professor, Pulmonary Sciences

Contact: dwight.klemm@cuanschutz.edu

University of Colorado webpage

Personal Statement
I have worked in adipocyte biology for over 25 years. During the first 14 years was focused on transcriptional regulation of adipogenesis and adipocyte survival. In 2004 I initiated studies to determine whether non-tissue resident progenitor cells traffic to adipose tissue and generate new adipocytes. My laboratory was the first to demonstrate that some adipocytes are produced from progenitors cells that have a hematopoietic rather than mesenchymal origin. We subsequently demonstrated that these unique adipocytes are 1) also produced in humans, 2) higher in female rather than male mice, 3) characterized by a proinflammatory, but low metabolic gene expression profile, and 4) produced from adipose tissue macrophage. Preliminary studies described in this proposal indicate that the highest number of these potentially detrimental adipocytes is found in pericardial adipose tissue. In 2009 I joined the faculty of the Gates Center for Center Regenerative Medicine and Stem Biology.

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Research Interest

 

I was a Research Biologist and Director of Basic Research for the Pulmonary and Critical Care Section of the Veterans Administration Eastern Colorado Health Care System (VA ECHCS) from 2001 to 2008, and currently serve as a Research Biologist in the Geriatric Research, Education and Clinical Center (GRECC) at the same VA facility since 2016. I am also a professor at the University of Colorado Anschutz Medical Campus where I serve as co-director of the Obesity Cell Biology Program of the Colorado Obesity Research Institute. In this capacity I have priority access to the institute’s Energy Balance Core, Metabolic Core and Cell Biology Core. I also serve as Associate Director of our Specialized Center of Research (SCOR) on aging, gonadal hormones and obesity. Given my expertise in adipocyte and stem cell biology, our initial description and continued characterization of bone marrow-derived adipocytes, and access to state-of-the-art core facilities at VA ECHCS and University of Colorado, my laboratory is uniquely suited to complete the proposed studies.

Dimensions profile: See publications, grant, datasets, patents and clinical trial information.

The following images visualize Dr. Klemm's work. The word cloud is drawn from publication titles. The research collaboration map shows research relationships (click the image to enlarge):

Dr. Klemm's publication titles indicate his primary work is care of Veterans
Word cloud from pub titles
Dr. Klemm's collaborations are primarily from the University of Colorado
Research collaboration map
The following research fields have been used to summarize Dr. Klemm's publications and grants. The categories are based on 100 publications and 9 grants.
Publications Grants
Genetics Nutrition
Lung Obesity
Diabetes Diabetes
Stem Cell Research Aging
Obesity Stem Cell Research
Stem Cell Research - Nonembryonic - Non-Human Clinical Research
Nutrition Prevention
Regenerative Medicine Estrogen
Prevention Regenerative Medicine
Cardiovascular Stem Cell Research - Nonembryonic - Non-Human

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Grants & Funding

Diminished Sex Hormone Levels Stimulate Production of Inflammatory Bone Marrow-Derived Adipocytes

Obesity is prevalent among US military Veterans and linked to an increased incidence of cardiovascular disease, diabetes, pulmonary disorders, and certain forms of cancer. As the veteran population ages, diminished production of the primary sex hormone, estrogen, promotes fat accumulation in menopausal women.
We discovered a subpopulation of adipocytes in humans and mice termed bone marrow-derived adipocytes (BMDAs) that exhibit an inflammatory character. These unique adipocytes are more abundant in female than male mice. They are increased by the loss of estrogen in female mice. These observations led us to hypothesize that BMDAs provide a link between sex hormone-related changes in adiposity and body-wide inflammation.
This project will test this hypothesis in mice in which estrogen signaling is suppressed and in which BMDAs and their progenitors are specifically ablated. Understanding the mechanisms by which sex hormones regulate BMDA and progenitor production holds the potential for therapies to prevent menopausal diseases in aging female veterans.
Investigator: Dwight Klemm
Funder: Veterans Affairs
NIH website
Publications of note:
Hematopoietic Stem Cell-Derived Adipocytes Modulate Adipose Tissue Cellularity, Leptin Production and Insulin Responsiveness in Female Mice
Hematopoietic stem cells produce intermediate lineage adipocyte progenitors that simultaneously express both myeloid and mesenchymal lineage markers in adipose tissue
Modulation of Energy Expenditure by Estrogens and Exercise in Women

Integrin signaling promotes production of adipocytes from hematopoietic cells

Obesity is a major medical problem for which there are few effective therapies.
This project will investigate the processes and events that control the production of potentially harmful fat cells. Successful completion of these studies will identify new targets for controlling the production of harmful fat-storing cells and prevent fat-related chronic disease.
Investigator: Dwight Klemm
Funder: National Institute of Diabetes and Digestive and Kidney Diseases
NIH website
Publications of note:
Hematopoietic Stem Cell-Derived Adipocytes Modulate Adipose Tissue Cellularity, Leptin Production and Insulin Responsiveness in Female Mice
Hematopoietic stem cells produce intermediate lineage adipocyte progenitors that simultaneously express both myeloid and mesenchymal lineage markers in adipose tissue

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Recent Publications

2022

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.
Learn more about this publication on Dimensions

2021

Strassheim D, Sullivan T, Irwin DC, Gerasimovskaya E, Lahm T, Klemm DJ, Dempsey EC, Stenmark KR, Karoor V. Metabolite G-Protein Coupled Receptors in Cardio-Metabolic Diseases. Cells. 2021 Nov 29;10(12):3347. doi: 10.3390/cells10123347.
PMID: 34943862.
Find more information on this paper from the Dimensions website

Gavin KM, Sullivan TM, Maltzahn JK, Rahkola JT, Acosta AS, Kohrt WM, Majka SM, Klemm DJ. Hematopoietic stem cells produce intermediate lineage adipocyte progenitors that simultaneously express both myeloid and mesenchymal lineage markers in adipose tissue. Adipocyte. 2021 Dec;10(1):394-407. doi: 10.1080/21623945.2021.1957290.
PMID: 34404315

Summers ME, Richmond BW, Menon S, Sheridan RM, Kropski JA, Majka SA, Taketo MM, Bastarache JA, West JD, De Langhe S, Geraghty P, Klemm DJ, Chu HW, Friedman RS, Tao YK, Foronjy RF, Majka SM. Resident mesenchymal vascular progenitors modulate adaptive angiogenesis and pulmonary remodeling via regulation of canonical Wnt signaling. FASEB J. 2020 Jun 13.
PMID: 32533805

Garat CV, Majka SM, Sullivan TM, Crossno JT, Reusch JEB, Klemm DJ. CREB depletion in smooth muscle cells promotes medial thickening, adventitial fibrosis and elicits pulmonary hypertension. Pulm Circ. 2020 Apr-Jun; 10(2):2045894019898374.
PMID: 32313640

Gewin LS, Summers ME, Harral JW, Gaskill CF, Khodo SN, Neelisetty S, Sullivan TM, Hopp K, Reese JJ, Klemm DJ, Kon V, Ess KC, Shi W, Majka SM. Inactivation of Tsc2 in Abcg2 lineage-derived cells drives the appearance of polycystic lesions and fibrosis in the adult kidney. Am J Physiol Renal Physiol. 2019 11 01; 317(5):F1201-F1210.
PMID: 31461347

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Current Grants

Diminished Sex Hormone Levels Stimulate Production of Inflammatory Bone Marrow-Derived Adipocytes

Grant number: I01BX005135
Start/End date: 4/1/2021 - 3/31/2025

Funder: United States Department of Veterans Affairs
NIH website: https://reporter.nih.gov/project-details/10017066

Bioenergetic and Metabolic Consequences of the Loss of Gonadal Function

Grant number: U54AG062319
Funding amount: $4,536,882.00
Start/End date: 9/20/2012 - 5/31/2023

Funder: National Institute on Aging
NIH website: https://reporter.nih.gov/project-details/10456782