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MICaB Faculty

Jeffery S. Miller
Jeffrey S. Miller, M.D.

Professor

Department of Medicine

Northwestern University School of Medicine, 1985, M.D.

612-625-7409 office
612-626-4217 lab

E-mail:mille011@umn.edu


Bio Statement:

Jeffrey Miller, M.D. serves as the Deputy Director of the Masonic Comprehensive Cancer Center (MCC) and as the Deputy Director of the Academic Health Center’s Clinical and Translational Sciences Institute (CTSI). He is also Director of the Cancer Experimental Therapeutics Initiative (CETI), a MCC program dedicated to support outstanding investigator initiated translational science, to increase accrual on early phase trials, to mentor junior faculty and to prioritize strategic investments into translational cancer research. Dr. Miller received a Bachelor of Science degree from Northwestern University in Evanston, Ill., and a doctorate of medicine from Northwestern University School of Medicine in 1985. He completed an internship and residency in internal medicine at the University of Iowa in Iowa City. After completing a postdoctoral fellowship in hematology-oncology at the University of Minnesota in 1991, he joined the faculty and is now a Professor of Medicine. In 2009, he was awarded the Roger L. and Lynn C. Headrick Family Chair in Cancer Therapeutics for his translational research.

Research Interests:

Natural killer (NK) cell development

Throughout his academic career Dr. Miller has been interested in NK cell biology. His laboratory is focused on understanding the mechanisms of NK cell development and determining how NK cell killer immunoglobulin receptor (KIR) acquisition affects NK cell function through a process referred to as NK cell education or licensing.  Most recently, he has been exploring the role of cytomegalovirus (CMV) reactivation after hematopoietic cell transplantation in enhancing NK cell reconstitution and function. CMV is the only virus known to induce the development of ”adaptive” NK cells with memory properties which are long lived and exhibit enhanced responses to subsequent exposures. Dr. Miller and his team have identified these adaptive NK cells in humans and determined that they have a methylation signature remarkably similar to that of CD8+ T cells.  His long-term goal is to translate these novel findings into better NK-cell based immunotherapies to treat cancer without the morbidity of CMV infection.

Targeted Immunotherapy to Treat Human Cancer

Dr. Miller was the first to report that related donor haploidentical allogeneic NK cells can expand after adoptive transfer and induce remission in patients with refractory leukemia.  Building on this landmark study, he spends significant effort developing novel methods to exploit NK cells therapeutically to treat infections, to cure cancer and to improve outcomes from allogeneic hematopoietic cell transplantation (HCT). He also leads a focused effort to understand the association of KIR immunogenetics with protection against relapse after allogeneic HCT. Dr. Miller and his team have demonstrated that transplants from donors with favorable KIR genes protect against relapse of acute myeloid leukemia after unrelated donor HCT.  He is currently testing novel strategies to activate NK cells in vivo (using novel proteins such as interleukin-15) and to create antigen-specific NK cells with Bispecific Killer Engagers (BiKEs), which are proteins that facilitate targeting of tumor antigens by NK cells.

Current Discovery & Research Themes in the Miller Laboratory:

  • NK cells and their receptors after hematopoietic cell transplantation
  • CMV induced adaptive NK cells exhibit enhanced function through CD16
  • Induction of NK cells antigen specificity through CD16 targeting      
  • Preserving and enhancing NK cell function through antibody dependent cellular cytotoxicy (ADCC)

 

Selected Recent Publications:

  • Bachanova V, Cooley S, Defor T, Verneris MR, Zhang B, McKenna D, Curtsinger J, Panoskaltsis-Mortari A, Lewis D, Hippen K, McGlave P, Weisdorf  D, Blazar B, Miller JS. 2014. Clearance of acute myeloid leukemia by haploidentical natural killer cells is improved using IL-2 dpitheria toxin fusion protein. Blood (Plenary Paper) 123(25):3855-63.
  • Gleason M, Ross J, Warlick E, Lund T, Verneris MR, Wiernik A, Spellman S, Haagenson MD, Lenvik, A, Litzow M, Blazar B, Burnette PK, Weiner L, Weisdorf D, Vallera DA, Miller JS. 2014. CD16xCD33 bispecific killer cell engager (BiKE) activates NK cells from MDS patients against primary MDS and MDSC CD33+ target. Blood 123(19):3016-26.
  • Cooley S, Weisdorf D, Guethlein LA, Klein J, Wang T, Marsh SGE, Spellman S, Haagenson M, Saeturn K, Ladner M, Trachtenberg E, Parham P, Miller J. 2014. Donor killer cell lg-like receptor B haplotypes, recipient HLA-C1, and HLA-C mismatch enhance the clinical benefit of unrelated transplantation for acute myelogenous leukemia. Journal of Immunology 15:192(10):4592-600.
  • Wiernik A, Foley B, Zhang B, Verneris MR, Warlick E, Gleason MK, Ross JA, Luo X, Weisdorf DJ, Walcheck B, Vallera DA, Miller JS:2013. Targeting natural killer cells to acute myeloid leukemia in vitro with a CD16 x 33 bispecific killer cell engager and ADAM17 inhibition. Clin Cancer Res. 2013 Jul 15;19(14):3844-55.
  • Romee R, Foley B, Lenvik T, Wang Y, Zhang B, Ankarlo D, Luo X, Cooley S, Verneris M, Walcheck, Miller JS. 2013. NK cell CD16 surface expression and function is regulated by a disintegrin and metalloprotease-17 (ADAM 17). Blood. 121(18): 3599-608.
  • Foley B, Cooley S, Verneris MR, Curtsinger J, Luo X, Waller EK, Anasetti C, Weisdorf D, Miller JS. 2013. Human Cytomegalovirus (CMV)-Induced Memory-like NKG2C+ NK Cells are Transplantable and Expand In Vivo in Response to Recipient CMV Antigen.  J Immunol, 189:5082-5088.
  • Cooley S, Weisdorf DJ, Guethlein LA, Klein JP, Wang T, Le CT, Marsh SGE, Geraghty D, Spellman S, Haagenson MD, Ladner M, Trachtenberg E, Parham P and Miller JS. 2010. Donor selection for natural killer cell receptor genes leads to superior survival after unrelated transplantation for acute myelogenous leukemia. Blood (Plenary Paper), 2411-2419.
  • Cichocki F, Lenvik T, Sharma N, Yun G, Anderson SK, Miller J. 2010. Cutting edge: KIR antisense transcripts are processed into a 28-base PIWI-like RNA in human NK Cells. J. Immunol., 185:2009-2012.
  • Miller, J.S. Soignier Y. Panoskaltsis-Mortari A., McNearney S.A., Yun G.H..,
    Fautsch S.K., McKenna D., Le C., Defor T.E., Burns L.J., Orchard P.J., Blazar B.R., Wagner J.E., Slungaard A., Weisdorf D.J., Okazaki I.J., McGlave P.B. 2005. Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in cancer patients. Blood, 105:3051-3057.
  • Miller JS, McCullar V. 2001. Human natural killer cells with polyclonal lectin and immunoglobulinlike receptors develop from single hematopoietic stem cells with preferential expression of NKG2A and KIR2DL2/L3/S2.  Blood 98:705-713.