Dr. Celestine (Celly) Wanjalla is a physician scientist in the Division of Infectious Diseases. She earned her undergraduate degree in Biological Sciences with a distinction in research from Cornell University in Ithaca, and her MD PhD in Immunology and Microbial pathogenesis at Thomas Jefferson University in Philadelphia. She was awarded the Jefferson Graduate School Award in Translational Medicine. She completed residency and fellowship training in Internal Medicine and Infectious Diseases at VUMC. She was awarded a Vanderbilt Scholars in HIV and Heart, Lung, Blood and Sleep Research (V-SCHoLARS) K12 award during her postdoctoral training with Dr. John Koethe studying Adipose Tissue T cells and endothelial cell dysfunction in people living with HIV. Her current research seeks to comprehensively define the role of virus-specific immune cells in the pathogenesis of atherosclerotic cardiovascular disease and other diseases of aging. When she is not in the laboratory, she enjoys hiking with her family, trying out new recipes and traveling.
Cardiovascular disease remains the leading cause of death globally despite advancements in the detection and mitigation of risk factors. Though inherently multifactorial, chronic immune activation and inflammation are key mediators of atherosclerotic cardiovascular disease and other comorbidities. Persons living with HIV have twice the risk of developing cardiovascular disease. Persistent exposure to HIV antigens and co-infection with chronic herpes viruses such as CMV or hepatitis B/C contribute to chronic inflammation in PWH and appear to be important in cardiovascular disease pathogenesis.
My lab has adopted a multidisciplinary approach to i) Define virus-specific innate and adaptive immune cells in the peripheral blood and coronary arteries of persons with cardiometabolic disease using existing multiparameter flow cytometry and single-cell techniques. ii) Optimize techniques to better understand the antigenic drivers of the adaptive immune response at the tissue level. Specifically, we design studies that link the viral reservoirs, virus-specific memory T cells, and epitope discovery. iii) Apply/Implement changes in cardiovascular disease risk assessment and therapeutic approaches to improve outcomes in patients.
Major research questions:
Virus-specific immune responses, chronic inflammation and aging
Our research focuses on how obesity and aging reshape immune responses and lead to inflammatory diseases. Immune cells are sensitive to their metabolic environment, which affects intracellular metabolism and signaling and fine-tune immune functions. We are interested in understanding how metabolic cues regulate communication between immune cells, focusing on dendritic cells and T cells. Our Lab studies how obesity and aging disturb the immune and metabolic balance and lead to excessive inflammation, including diseases such as psoriasis and asthma. We decode molecular mechanisms that link dendritic cell metabolism to tissue inflammation by combining mouse models of inflammatory skin and lung diseases with systems immunology approaches.
Select Publications:
Mogilenko DA*, Shchukina I*, Artyomov MN. Immune ageing at single-cell resolution. Nat Rev Immunol 22, 484–498 (2022). https://doi.org/10.1038/s41577-021-00646-4 (*co-first authors)
Mogilenko DA, Shpynov O, Andhey PS, Arthur L, Swain A, Esaulova E, Brioschi S, Shchukina I, Kerndl M, Bambouskova M, Yao Z, Laha A, Zaitsev K, Burdess S, Gillfilan S, Stewart SA, Colonna M, Artyomov MN. Comprehensive profiling of an aging immune system reveals clonal GZMK+ CD8 T cells as conserved hallmark of inflammaging. Immunity 54(1):99-115.e12 (2021). https://doi.org/10.1016/j.immuni.2020.11.005
Brioschi S*, Wang W-L*, Peng V*, Wang M, Shchukina I, Greenberg ZJ, Bando JK, Jaeger N, Czepielewski RS, Swain A, Mogilenko DA, Beatty WL, Bayguinov P, Fitzpatrick JAJ, Schuettpelz LG, Fronick CC, Smirnov I, Kipnis J, Shapiro VS, Wu GF, Gilfillan S, Cella M, Artyomov MN, Kleinstein SH, Colonna M. Heterogeneity of meningeal B cells reveals a lymphopoietic niche at the CNS borders. Science 373(6553):eabf9277 (2021). https://www.science.org/doi/10.1126/science.abf9277 (*co-first authors)
Arthur L*, Esaulova E*, Mogilenko DA, Tsurinov P, Burdess S, Laha A, Presti R, Goetz B, Watson MA, Goss CW, Gurnett CA, Mudd PA, Beers C, O’Halloran JA & Artyomov MN. Cellular and plasma proteomic determinants of COVID-19 and non-COVID-19 pulmonary diseases relative to healthy aging. Nature Aging 1, 535-549 (2021). https://doi.org/10.1038/s43587-021-00067-x (*co-first authors)
Bambouskova M, Potuckova L, Paulenda T, Kerndl M, Mogilenko DA, Lizotte K, Swain A, Hayes S, Sheldon RD, Kim H, Kapadnis U, Ellis AE, Isaguirre C, Burdess S, Laha A, Amarasinghe GK, Chubukov V, Roddy TP, Diamond MS; Jones RJ, Simons DM, Artyomov MN. Itaconate confers tolerance to late inflammasome activation. Cell Reports 34(10):108756 (2021). https://doi.org/10.1016/j.celrep.2021.108756
Mogilenko DA, Haas JT, L'homme L, Fleury S, Quemener S, Levavasseur M, Becquart C, Wartelle J, Bogomolova A, Pineau L, Molendi-Coste O, Lancel S, Dehondt H, Gheeraert C, Melchior A, Dewas C, Nikitin A, Pic S, Rabhi N, Annicotte JS, Oyadomari S, Velasco-Hernandez T, Cammenga J, Foretz M, Viollet B, Vukovic M, Villacreces A, Kranc K, Carmeliet P, Marot G, Boulter A, Tavernier S, Berod L, Longhi MP, Paget C, Janssens S, Staumont-Sallé D, Aksoy E, Staels B, Dombrowicz D. Metabolic and innate immune cues merge into a specific inflammatory response via the UPR. Cell 177(5):1201-1216 (2019). https://doi.org/10.1016/j.cell.2019.03.018
Haas JT*, Vonghia L*, Mogilenko DA*, Verrijken A, Molendi-Coste O, Fleury S, Deprince A, Nikitin A, Woitrain E, Ducrocq-Geoffroy L, Pic S, Derudas B, Dehondt H, Gheeraert C, Van Gaal L, Driessen A, Lefebvre P, Staels B, Francque S, Dombrowicz D. Transcriptional network analysis implicates altered hepatic immune function in NASH development and resolution. Nature Metabolism 1(6):604-614 (2019). https://doi.org/10.1038/s42255-019-0076-1 (*co-first authors)
Devos M*, Mogilenko DA*, Fleury S, Gilbert B, Becquart C, Quemener S, Dehondt H, Tougaard P, Staels B, Bachert C, Vandenabeele P, Van Loo G, Staumont-Salle D, Declercq W, Dombrowicz D. Keratinocyte expression of A20/TNFAIP3 controls skin inflammation associated with atopic dermatitis and psoriasis. J Invest Dermatol 139(1):135-145 (2019). https://doi.org/10.1016/j.jid.2018.06.191 (*co-first authors)
Immunometabolism in obesity and aging
