Sakeen W. Kashem
Entering Class: 2010
New York University
Chemistry major, Mathematics minor
University of Minnesota
Microbiology, Immunology and Cancer Biology Graduate Program
Honors and Awards:
- Beatrice Z. Milne and Theodore Brandenburg Award, 2016
MSTP Student Governance:
- Student Advisory Committee, 2012-2014, co-chair 2012-13
Thesis Advisor: Dan Kaplan, M.D., Ph.D.
The mechanism by which the cutaneous dendritic cells (DCs) induce and regulate the differentiation of naïve CD4+ T cells along the T helper-17 (TH17) lineage is expansive and not well understood. Antigen presenting cells (APCs), such as the epidermal Langerhans cells (LCs) and the dermal dendritic cells (dDCs), encounter pathogens in the periphery and migrate to the lymph node where they present processed antigen to CD4+ T helper cells or CD8+ cytotoxic T lymphocytes (CTLs) to induce adaptive immune responses. In addition to direct interaction, the fate of each individual helper T cell lineage also requires specific cytokines secreted by the respective APC subtype. The knowledge of what cell types and which cytokines are necessary for the positive and negative regulation of the lineage commitment is clearly ill defined. In addition, there is a limited amount of resources that can systemically elucidate the networking of the cutaneous immune system in vivo. My research focuses on CD11b+ dermal dendritic cells, which make up for majority of the migratory DCs in the skin. Using novel mouse lines and an established Candida albicans infection model, we will systematically investigate the role of this dendritic cell subset in shaping adaptive immunity.
Kashem SW, Haniffa M, Kaplan DH. Antigen-Presenting Cells in the Skin. Annu Rev Immunol. 2017 Apr 26;35:469-499.
Wiesner DL, Smith KD, Kashem SW, Bohjanen PR, Nielsen K. Different Lymphocyte Populations Direct Dichotomous Eosinophil or Neutrophil Responses to Pulmonary Cryptococcus Infection. J Immunol. 2017 Feb 15;198(4):1627-1637.
Kashem SW, Kaplan DH. Skin Immunity to Candida albicans. Trends Immunol. 2016 Jul;37(7):440-50. Review. PMCID: PMC4931795
Mohammed J, Beura LK, Bobr A, Astry B, Chicoine B, Kashem SW, Welty NE, Igyártó BZ, Wijeyesinghe S, Thompson EA, Matte C, Bartholin L, Kaplan A, Sheppard D, Bridges AG, Shlomchik WD, Masopust D, Kaplan DH. Stromal cells control the epithelial residence of DCs and memory T cells by regulated activation of TGF-β. Nat Immunol. 2016 Apr;17(4):414-21.
Auger JL, Cowan HM, Engelson BJ, Kashem SW, Prinz I, Binstadt BA. Arthritis in KRN T cell receptor transgenic mice does not require interleukin-17 or Th17 cells. Arthritis Rheumatol. 2016 Aug;68(8):1849-55.
Linehan JL, Dileepan T, Kashem SW, Kaplan DH, Cleary P, Jenkins MK. Generation of Th17 cells in response to intranasal infection requires TGF-β1 from dendritic cells and IL-6 from CD301b+ dendritic cells. Proc Natl Acad Sci U S A. 2015 Oct 13;112(41):12782-7. PMCID: PMC4611596
Kashem SW, Riedl MS, Yao C, Honda CN, Vulchanova L, Kaplan DH. Nociceptive Sensory Fibers Drive Interleukin-23 Production from CD301b+ Dermal Dendritic Cells and Drive Protective Cutaneous Immunity. Immunity. 2015 Sep 15;43(3):515-26. PMCID: PMC4607048
Kashem SW, Igyártó BZ, Gerami-Nejad M, Kumamoto Y, Mohammed J, Jarrett E, Drummond RA, Zurawski SM, Zurawski G, Berman J, Iwasaki A, Brown GD, Kaplan DH. Candida albicans Morphology and Dendritic Cell Subsets Determine T Helper Cell Differentiation. Immunity. 2015 Feb 17;42(2):356-66. PMCID: PMC4343045
Cabrera-Perez J, Condotta SA, James BR, Kashem SW, Brincks EL, Rai D, Kucaba TA, Badovinac VP, Griffith TS. Alterations in antigen-specific naive CD4 T cell precursors after sepsis impairs their responsiveness to pathogen challenge. J Immunol. 2015 Feb 15;194(4):1609-20. PMCID: PMC4412277
Haley K, Igyarto BZ, Ortner D, Bobr A, Kashem S, Schenten D, Kaplan DH. Langerhans cells require MyD88-dependent signals for Candida albicans response but not for contact hypersensitivity or migration. J Immunol. 2012;188:4334-4339. PMCID: PMC3331889
For work prior to entering the U of MN MSTP:
Kashem SW, Subramanian H, Collington SJ, Magotti P, Lambris JD, Ali H. G protein coupled receptor specificity for C3a and compound 48/80-induced degranulation in human mast cells: roles of Mas-related genes MrgX1 and MrgX2. Eur J Pharmacol. 2011 Oct 1;668(1-2):299-304. PMCID: PMC3169012
Subramanian H, Kashem SW, Collington SJ, Qu H, Lambris JD, Ali H. PMX-53 as a dual CD88 antagonist and an agonist for Mas-related gene 2 (MrgX2) in human mast cells. Mol Pharmacol. 2011 Jun;79(6):1005-13. PMCID: PMC3102546
Hassan S, Sainz IM, Khan MM, Bradford HN, Isordia-Salas I, Kashem SW, Sartor RB, Colman RW. Antithrombotic activity of kininogen is mediated by inhibitory effects of domain 3 during arterial injury in vivo. Am J Physiol Heart Circ Physiol. 2007 Jun;292(6):H2959-65.