Alfred L.M. Bothwell, PhD

Professor of Immunobiology
Professor of Bio5
Professor of Genetics GIDP
Professor of Cancer Biology GIDP

Dr. Bothwell received his AB from Washington University and his PhD from Yale University in Sidney Altman’s lab studying RNA biogenesis in bacteria and human cells.  He did postdoctoral research at MIT in David Baltimore’s lab where he developed molecular probes for antibody genes and defined molecular properties of the murine antibody response and their genes.  He joined the Yale Medical School faculty and has studied basic properties of lymphocytes and their receptors in mouse models of infection, autoimmunity, transplantation and novel humanized mouse models of vascular disease, type 1 diabetes and cancer. Studies of human complement regulation by CD59 lead to intellectual property that was the basis for founding Alexion Pharmaceuticals.  He has published over 190 papers and reviews on his research.

Cancer Focus 

Current studies are focused on the immunoregulatory properties of regulatory T cells, myeloid derived suppressor cells and other lymphocytes in immune responses to cancer in both mice and human models. The roles of Wnt ligands DKK1 and DKK2 in regulating the development of tumors is studied in mouse models and in human patient derived xenograft models.  Organoids are being used to define mechanisms of tumor development from stem cells and formation of tumor microenvionmental niches. New insight is being developed from studies of lymphocytes from the same patient as tumors growing in humanized mice. These strategies can be used to evaluate candidate drug therapies and cellular properties in vivo. 

  • A.B.; Washington University
  • PhD; Yale University
  • Postdoctoral Fellow: MIT and Cold Spring Harbor

Recent Publications


Shin, J. Hun, J. Jeong, J. Choi, J. Lim, R. K. Dinesh, J. Braverman, J. Young Hong, S. E. Maher, M. C. Amezcua Vesely, WJ. Kim, et al., "Dickkopf-2 regulates the stem cell marker LGR5 in colorectal cancer via HNF4α1.", iScience, vol. 24, issue 5, pp. 102411, 2021 May 21. PMCID: PMC8099562  PMID: 33997693
van den Pol, A. N., X. Zhang, S. E. Maher, and A. L. M. Bothwell, "Immune cells enhance Zika virus-mediated neurologic dysfunction in brain of mice with humanized immune systems.", Dev Neurobiol, vol. 81, issue 4, pp. 389-399, 2021 May. PMID: 33811750
Shin, J. Hun, J. Jeong, S. E. Maher, H-W. Lee, J. Lim, and A. L. M. Bothwell, "Colon cancer cells acquire immune regulatory molecules from tumor-infiltrating lymphocytes by trogocytosis.", Proc Natl Acad Sci U S A, vol. 118, issue 48, 2021 Nov 30. PMCID: PMC8640789  PMID: 34819374
Paluri, S. L., M. Burak, A. G. Senejani, M. Levinson, T. Rahim, K. Clairmont, M. Kashgarian, I. Alvarado-Cruz, R. Meas, M. Cardó-Vila, et al., "DNA glycosylase deficiency leads to decreased severity of lupus in the Polb-Y265C mouse model.", DNA Repair (Amst), vol. 105, pp. 103152, 2021 Sep. PMID: 34186496


Jayakumar, A., and A. L. M. Bothwell, "RIPK3-Induced Inflammation by I-MDSCs Promotes Intestinal Tumors.", Cancer Res, vol. 79, issue 7, pp. 1587-1599, 2019 04 01. PMCID: PMC7395226  PMID: 30786994
Chae, W-J., and A. L. M. Bothwell, "Dickkopf1: An immunomodulatory ligand and Wnt antagonist in pathological inflammation.", Differentiation, vol. 108, pp. 33-39, 2019 Jul - Aug. PMCID: PMC6982462  PMID: 31221431
Jayakumar, A., and A. L. M. Bothwell, "Functional Diversity of Myeloid-Derived Suppressor Cells: The Multitasking Hydra of Cancer.", J Immunol, vol. 203, issue 5, pp. 1095-1103, 2019 09 01. PMCID: PMC6703177  PMID: 31427398


Chae, W-J., and A. L. M. Bothwell, "Therapeutic Potential of Gene-Modified Regulatory T Cells: From Bench to Bedside.", Front Immunol, vol. 9, pp. 303, 2018. PMCID: PMC5820299  PMID: 29503652
Xiao, Q., J. Wu, W-J. Wang, S. Chen, Y. Zheng, X. Yu, K. Meeth, M. Sahraei, A. L. M. Bothwell, L. Chen, et al., "DKK2 imparts tumor immunity evasion through β-catenin-independent suppression of cytotoxic immune-cell activation.", Nat Med, vol. 24, issue 3, pp. 262-270, 2018 03. PMCID: PMC5840007  PMID: 29431745
Moon, J-S., C. Hee Mun, J-H. Kim, J-Y. Cho, S-D. Park, T-Y. Park, J-S. Shin, C-C. Ho, Y-B. Park, S. Ghosh, et al., "Intranuclear delivery of the transcription modulation domain of Tbet-improved lupus nephritis in (NZB/NZW) F1 lupus-prone mice.", Kidney Int, vol. 93, issue 5, pp. 1118-1130, 2018 05. PMID: 29409726