THE INFLUENCE OF EXERCISE, MENTAL STRESS, AND OBESITY ON IMMUNE AND HORMONAL PARAMETERS

My primary research experience during my Master’s degree was under the direction of Dr. Lee Franco at Virginia Commonwealth University (VCU). Our research aimed to determine the effects of obesity on the secondary responses to exercise and mental stress. Interestingly, in our population of relatively healthy young college aged males, there was little effect of obesity. This project sparked my interest in immunology, specifically the interplay between inflammation and obesity.

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1. Crabb E.B., Bowen M.K, Huang C.J., Caslin H.L., Acevedo E.O., Franco R.L. G protein-coupled receptor kinase-2 in peripheral blood mononuclear cells following acute mental stress. Life Sciences. 2016; 145:184-9. doi: 10.1016/j.lfs.2015.12.035

2. Caslin H.L., Crabb E.B, Huang C.J., Bowen M.K, Acevedo E.O., Franco R.L. The effect of obesity on inflammatory cytokine and leptin production following acute mental stress. Psychophysiology. 2016; 53(2):151-8. doi: 10.1111/psyp.12568

3. Crabb E.B., Franco R.L., Caslin H.L., Blanks A.M., Bowen M.K, Acevedo E.O. The effect of physical and mental stress on soluble adhesion molecule concentrations. Life Sciences. 2016 May 31. pii: S0024-3205(16)30341-1. doi: 10.1016/j.lfs.2016.05.042.

LACTIC ACID INHIBITS MAST CELL METABOLISM AND INFLAMMATORY FUNCTION

When I started my doctoral degree, my advisor (John Ryan, VCU) was interested in the effects of lactic acid on mast cell activation. I was familiar with lactic acid in exercise and cell metabolism, and was able to focus my dissertation work on this project. Lactic acid is elevated in many diseases, including sepsis and allergic disease. This work was the first to suggest a mechanistic link between elevated levels of lactic acid and increased mortality that have been shown numerous times in sepsis patients. We hypothesize that lactic acid is a negative regulator of cell metabolism that fuels immune activation, contributing to secondary immunosuppression in sepsis. Additionally, this work sparked my interest in innate immune cell immunometabolism, which I am now studying further during my postdoctoral fellowship.

4. Abebayehu D., Spence A.J., Abdul Qayum A. Taruselli M., McLeod J., Caslin H.L., Kolawole E., Ndaw V., Barnstein B.O., Oskertizian C.A., Ryan J.J. Lactic acid suppresses IL-33-mediated mast cell inflammatory responses via HIF-1 dependent miR-155 suppression. Journal of Immunology. 2016; 197(7):2909-17. doi: 10.4049/jimmunol.1600651

5. Caslin H.L., Taruselli M.T., Haque T.T., Pondicherry N., Baldwin E.A., Barnstein B.O., Ryan J.J. Inhibiting glycolysis and ATP production attenuates IL-33-mediated cytokine production in mast cells and IL-33-induced peritonitis. Frontiers in Immunology. 2018; 9. doi:10.3389/fimmu.2018.03026

6. Abebayehu D., Spence A.J., Caslin H.L., Taruselli M.T., Kolawole E.M., Chumanevich A.P., Sell S., Oskeritzian C.A., Ryan J.J. Lactic acid suppresses IgE-mediated mast cell function in vitro and in vivo. Cell Immunology. 2019 Jul;341:103918. doi: 10.1016/j.cellimm.2019.04.006.

7. Caslin H.L., Abebayehu D., Abdul Qayum A., Paez P.A., Hoeferlin L.A., Chalfant C.E., Ryan JJ. Lactic acid limits glycolysis and ATP availability effectively reducing LPS-induced cytokine production in mast cells and in vivo. Journal of Immunology. 2019 Jul 15;203(2):453-464. doi: 10.4049/jimmunol.1801005.

DIDOX SUPPRESSES MAST CELL RESPONSES IN ALLERGIC DISEASE

During my PhD, my advisor, Dr. John Ryan, formed a collaboration with Dr. Howard Elford to determine the potential uses for Didox beyond its intended use for cancer treatment. Our research found that this ribonucleotide reductase inhibitor can act as an antioxidant to suppress allergic activation of mast cells by IgE and IL-33.

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8. McCleod J.,1 Caslin H.L.1, Spence A.J., Elford H., Ryan J.J. Didox (3,4-dihydroxybenzohydroxamic acid) suppresses IgE-mediated mast cell activation through attenuation of NFκB and AP-1 transcription in primary mouse cells. Cellular Immunology. 2017 Dec; 322:41-48. doi: 10.1016/j.cellimm.2017.09.008

1co-first authorship

9. Caslin H.L.,1 McCleod J.,1 Spence A.J., Abdul Qayum A., Kolawole E.M., Taruselli M, Paranjape A., Elford H., Ryan J.J. Didox (3,4-dihydroxybenzohydroxamic acid) suppresses IL-33-induced cytokine production in primary mouse mast cells. Cellular Immunology. 2017 Sep; 319:10-16. doi: 10.1016/j.cellimm.2017.04.013

1co-first authorship

REVIEW ARTICLES AND ADDITIONAL CO-AUTHOR PROJECTS FROM PHD

The primary theme of research in my PhD lab was to understand the signaling mechanisms responsible for shaping mast cell responses in different tissues or disease microenvironments. Here are publications from additional projects that I was able to help with and collaborative lab efforts towards review articles.

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10. Caslin H.L., Taruselli M.T., Paranjape A., Kiwanuka K., Haque T., Oskeritzian C.A., Ryan J.J. The Use of Human and Mouse Mast Cell and Basophil Cultures to Assess Type 2 Inflammation. Methods Mol Biol. 2018;1799:81-92. doi: 10.1007/978-1-4939-7896-0_8.

11. Caslin H.L., Kiwanuka K.N., Haque T.T., Taruselli M.T., MacKnight H.P., Paranjape A., Ryan J.J. Controlling Mast Cell Activation and Homeostasis: Work Influenced by Bill Paul that Continues Today.

Frontiers in Immunology. 2018 Apr; 9: 868. doi:10.3389/fimmu.2018.00868

12. Ndaw V., Abebayehu D., Spence A.J., Paez P.A., Kolawole E.M., Taruselli M., Caslin H.L., Chumanevich A.P., Paranjape A., Baker B., Barnstein B.O., Haque T.T., Kiwanuka K.N., Oskertizian C.A., Ryan J.J. TGFβ1 Suppresses IL-33-induced Mast Cell Activation. Journal of Immunology. 2017 Aug 1;199(3):866-873. doi: 10.4049/jimmunol.1601983.

13. Abdul Qayum A., Paranjape A., Abebayehu D., Kolawole E.M., Haque T.T., McLeod J.J.A., Spence J.A., Caslin H.L., Baker B., Taruselli M.T., Oskeritzian C.A., Ryan J.J. IL-10-induced miR-155 targets SOCS1 to enhance IgE-mediated mast cell activation and passive systemic anaphylaxis in mice. Journal of Immunology. 2016; 196(11):4457-67. doi: 0.4049/jimmunol.1502240

V. Immunometabolism in obesity (Postdoc lab): I am now working at Vanderbilt University with Dr. Alyssa Hasty. Our lab studies the influence of obesity on immune cells in adipose tissue and conversely, the influence of immune cells on obesity-associated diseases such as diabetes. I am the first author on an

IMMUNOMETABOLISM IN OBESITY

I am now working at Vanderbilt University with Dr. Alyssa Hasty. Our lab studies the influence of obesity on immune cells in adipose tissue and conversely, the influence of immune cells on obesity-associated diseases such as diabetes. Thus far, I have written two reviews focused on macrophage immunometabolism in obesity.

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14. Caslin H.L and Hasty A.H. Obesity and Immunometabolism: Perspectives on Future Research and Therapeutic Development. Current Obesity Reports. 2019 Sep;8(3):210-219. doi: 10.1007/s13679-019-00344-2.

15. Caslin H.L*, Bhanot M.*, Bolus W.R., and Hasty A.H. Adipose tissue macrophages: unique polarization and bioenergetics in obesity. Immunological Reviews. Invited Review, Submitted January 18, 2020.