Celestine Wanjalla, MD, PhD

Celestine
Wanjalla MD, PhD
Assistant Professor of Medicine

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.

https://wag.app.vanderbilt.edu/PublicPage/Faculty/Details/45224

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:

  • What is the role of chronic herpes and other viral infections in the pathogenesis of CVD? Do viral antigens expressed in coronary plaques contribute to residual cardiovascular risk?

  • Is there synergy between viral antigens and lipids in the stimulation of adaptive immune cells within coronary plaque? Does this modify the viral epitopes?

  • Can we reduce the burden of residual CVD risk and improve clinical outcomes by targeting viral reservoirs and/or anti-viral cells of the immune system?

Publications on PubMed.gov

celestine.wanjalla@vumc.org

Virus-specific immune responses, chronic inflammation and aging

Monkeypox – what do we know about the virus, and how can we treat the disease?

Casey Butrico
October 10, 2022
Monkeypox – what do we know about the virus, and how can we treat the disease? The monkeypox virus has been studied, and its mechanism of replicating and invading human cells are understood. Due to prior research on orthopoxviruses, there is a test currently available for diagnosing monkeypox. Additionally, antiviral therapies are currently under investigation. Finally, a monkeypox vaccine is approved and available for individuals at high risk for contracting the virus. While monkeypox treatment options continue to be studied, a variety of medical resources currently exist for high-risk individuals as well as those who were recently exposed to monkeypox.

Denis Mogilenko, PhD

Denis
Mogilenko, PhD
Assistant Professor of Medicine
Assistant Professor of Pathology, Microbiology, and Immunology
  • PhD: Institute for Experimental Medicine, Saint Petersburg, Russia
  • Postdoctoral Fellow: French Institute of Health and Medical Research (INSERM)
  • Postdoctoral Fellow: Washington University School of Medicine in St. Louis
https://wag.app.vanderbilt.edu/PublicPage/Faculty/Details/49015

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.

Publications on PubMed.gov

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)

denis.mogilenko@vumc.org

Immunometabolism in obesity and aging

Monkeypox – symptoms, transmission, and prevention

Casey Butrico
October 3, 2022
Monkeypox – symptoms, transmission, and prevention. Since the 1970s, there has been a steady rise in monkeypox virus cases. While the Orthopoxvirus genus is no stranger to the United States, the specific virus responsible for the monkeypox outbreak has largely been found in African countries, until recently. The geographic footprint of the virus and age of those contracting the disease has steadily expanded. While the epidemiology and symptoms associated with monkeypox are complex, the Centers for Disease Control (CDC) and World Health Organization (WHO) have multiple resources to educate us on the disease progression and modes of transmission.

Kelly E. Dooley, MD, PhD, MPH

Kelly
E.
Dooley, MD, PhD, MPH
Director, Division of Infectious Diseases
Professor of Medicine
Professor of Pathology, Microbiology and Immunology

Kelly Dooley, MD, PhD, MPH, is a Professor of Medicine, and Director of the Division of Infectious Disease within the Department of Medicine at Vanderbilt University Medical Center (VUMC).

As an infectious disease specialist and clinical pharmacologist, Dr. Dooley maintains an active clinical practice in HIV care. Her research focuses on tuberculosis therapeutics with an emphasis on clinical trials of TB drugs and HIV/TB co-treatment, as well as clinical pharmacology of TB and HIV drugs. She is lead investigator for trials of therapeutics for drug-sensitive and drug-resistant TB, TB-HIV, and pediatric TB meningitis. She is on the TB scientific committees of the AIDS Clinical Trials Group and IMPAACT networks, and is a consultant to World Health Organization on TB therapeutics and pharmacology.

Dr. Dooley earned her Master of Public Health in Epidemiology from University of North Carolina at Chapel Hill, and her medical degree from Duke University. She completed her Internal Medicine residency, and fellowships in Infectious Diseases and Clinical Pharmacology at Johns Hopkins University. She subsequently earned a PhD in Clinical Investigation at the Johns Hopkins Bloomberg School of Public Health. She joined VUMC in 2022, and is board certified in internal medicine and infectious diseases.

https://medicine.vumc.org/divisions/infectious-diseases

Rifat, D; Prideaux, B; Savic, RM; Urbanowski, ME; Parsons, TL; Luna, B; Marzinke, MA; Ordonez, AA; Demarco, VP; Jain, SK; Dartois, V; Bishai, WR; Dooley, KE. Using rabbits with cavitary disease and translational PK/PD modeling to understand TB trial results. Science Translational Medicine (2018) 10: eaai7786. PMC5969904.

Dooley, KE; Miyahara, S; von Groote-Biglingmaier, F; Sun, X; Hafner, R; Rosenkranz, SL; Ignatius, EH; Nuermberger, EL; Moran, L; Donahue, K; Swindells, S; Vanker, N; Diacon, AH; and the A5312 Study Team. Early Bactericidal Activity of Different Isoniazid Doses for Drug Resistant TB (INHindsight): A Randomized Open-label Clinical Trial. American Journal of Respiratory and Critical Care Medicine (2020) 201: 1579-1580.

Dooley KE, Rosenkranz SL, Conradie F, Moran L, Hafner R, von Groote-Bidlingmaier F, Lama J, Shenje J, de los Rios J, Comins K, Morganroth J, Diacon A, Cramer YS, Donahue K, Maartens G, and the AIDS Clinical Trials Group (ACTG) A5343 DELIBERATE Study Team. QT effects of bedaquiline, delamanid or both in patients with rifampicin–resistant TB: a randomized controlled trial. Lancet Inf Dis, (2021) 21: 975-983

Dorman SE, Nahid P, Kurbatova EV, Phillips PPJ, Bryant K, Dooley KE, Engle M, Goldberg SV et al. ACTG/TBTC. Four-month rifapentine regimens with or without moxifloxacin for tuberculosis. New England Journal of Medicine, (2021) 384: 1705-1718.

Svensson, EM; Aweeka , F; Park, J-G; Marzan, F; Dooley, KE*§; Karlsson, MO* Model-based estimates of the effects of efavirenz on bedaquiline pharmacokinetics and suggested dose adjustments for patients co-infected with HIV and tuberculosis. Antimicrobial Agents and Chemotherapy (2013) 57: 2780-2787. PMC3716161.

Dooley, KE; Luetkemeyer, AF; Park, J-G; Allen, R; Cramer, Y; Murray, S; Sutherland, D; Aweeka, F; Koletar, SL; Marzan, F; Bao, J; Savic R; Haas, DW; ACTG A5306 Study Team. Phase I safety, PK, and pharmacogenetics study of the anti-TB drug PA-824 with concomitant lopinavir/ritonavir, efavirenz, or rifampin. Antimicrobial Agents Chemotherapy (2015) 58: 5245-52. PMC4135849.

Dooley, KE; Kaplan, R; Mwelase, N; Grinsztejn, B; Ticona, E; Lacerda, M; Sued, O; Belonosova, E; Ait-Khaled, M; Angelis, K; Brown, D; Singh, R; Talarico, CL; Tenorio, AR; Keegan, MR; Aboud, M; and the INSPIRING study group. Dolutegravir-based antiretroviral therapy for patients co-infected with tuberculosis and HIV: a multicenter, noncomparative, open-label, randomized trial. Clin Inf Diseases 2020; 70(4):549-556.

Dooley, KE; Savic, R; Gupte, A; Marzinke, MA; Zhang, N; Edward, VA; Wolf, L; Sebe, M; Likoti, J; Fyvie, MJ; Shibambo, I; Beattie, T; Chaisson, RE; Churchyard, GJ; DOLPHIN Study Team. Once-weekly rifapentine and isoniazid for tuberculosis prevention in patients withHIV taking dolutegravir-based antiretroviral therapy: a phase I/II trial. Lancet HIV 2020. 7: e401-e409

Dooley, KE; Denti, P; Martinson, N; Cohn, S; Mashabela, F; Hoffmann, J; Haas, DW, Hull, J; Msandiwa, R; Castel, S; Wiesner, L; Chaisson, RE, McIlleron, H. Pharmacokinetics of efavirenz and treatment of HIV-1 among pregnant women with and without tuberculosis co-infection. Journal of Infectious Diseases (2015) 211: 197-205. PMC4334832.

McIlleron, H; Denti, P; Cohn, S; Mashabela, F; Hoffmann, J; Shembe, S; Msandiwa, R; Wiesner, L; Velaphi, S; Lala, S; Chaisson, R; Martinson, N; Dooley, KE. Prevention of tuberculosis using rifampicin plus isoniazid reduces nevirapine concentrations in HIV-exposed infants. Journal of Antimicrobial Chemotherapy (2017) 72: 2028-2034. PMC5890683.

Mathad JS, Savic R, Britto P, Jayachandran P, Wiesner L, Montepiedra G, Norman J, Zhang N, Townely E, Chakhtoura N, Bradford S, Patil S, Popson S, Chipato T, Rouzier V, Langat D, Chalermchockcharoentkit A, Kamthunzi P, Gupta A, Dooley KE: IMPAACT 2001 Study Team. Pharmacokinetics and safety of three months of weekly rifapentine and isoniazid for tuberculosis prevention in pregnant women. Clin Inf Dis, in press.

Paradkar, MS; D, BD; Mvalo, T; Arenivas, A; Thakur, KT; Wolf, L; Nimkar, S; Inamdar, S; Giridharan, P; Selladurai, E; Kinikar, A; Valvi, C; Khwaja, S; Gadama, D; Balaji, S; Kattagoni, KY; Venkatesan, M; Savic, R; Swaminathan, S; Gupta, A; Gupte, N; Mave, V; Dooley KE; for the TBM-KIDS Study Team. Randomized clinical trial of high dose rifampicin with or without levofloxacin versus standard of care for paediatric tuberculous meningitis: the TBM-KIDS Trial. Clin Inf Dis, in press.

More publications on PubMed.gov

kelly.e.dooley@vumc.org
RSS: