Jeffrey Miller, MD
Professor of Medicine; Deputy Director, University of Minnesota Cancer Center; Roger L. and Lynn C. Headrick Chair in Cancer Therapeutics
Hematologist / Oncologist
- Blood Cancer
- Blood and Marrow Transplantation
- Blood and Marrow Transplant
- Masonic Cancer Clinic
Northwestern University Medical School
University of Iowa
University of Minnesota
E: Stephanie Weiland
P: (612) 626-4024
F: (612) 626-3941
Division of Hematology, Oncology and Transplantation
420 Delaware Street SE, MMC 480
Minneapolis, MN 55455
Jeffrey S. Miller, MD, received a Bachelor of Science degree from Northwestern University in Evanston, Illinois and received his MD from Northwestern University School of Medicine. He completed an internship and residency in Internal Medicine at the University of Iowa in Iowa City. After completing a post-doctoral fellowship in Hematology, Oncology and Transplantation at the University of Minnesota, he joined the faculty in 1991. Dr. Miller is currently a Professor of Medicine at the University of Minnesota. He is the Deputy Director of the University of Minnesota Masonic Comprehensive Cancer Center. He has more than 20 years of experience studying the biology of NK cells and other immune effector cells and their use in clinical immunotherapy with over 170 peer-reviewed publications. He is a member of numerous societies such as the American Society of Hematology, the American Association of Immunologists, a member of the American Society of Clinical Investigation since 1999. He serves on the editorial board for Blood and is a reviewer for a number of journals and NIH grants.
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)
Dr. Miller has recently been awarded the Distinguished Research Lecture Award
- Miller JS, McCullar V. Human NK cells with polyclonal lectin and immunoglobulin receptors develop from single HSC’s with preferential expression of NKG2A and KIR2DL2/L3/S2. Blood. 98:705-713, 2001.
- Miller JS, Soignier Y, Panoskaltsis-Mortari A, McNearney SA, Yun GH, Fautsch SK, McKenna D, Le C, Defor TE, Burns LJ, Orchard PJ, Blazar BR, Wagner JE, Slungaard A, Weisdorf DJ, Okazaki IJ, McGlave PB. Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in cancer patients. Blood. 105:3051-3057, 2005.
- Cichocki F, Lenvik T, Sharma N, Yun G, Anderson SK, Miller JS: KIR Antisense Transcripts are Processed into a 28 Base PIWI-like RNA in Human NK Cells. Journal of Immunology (Cutting Edge), 185:2009-2012, 2010.
- 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: Donor selection for natural killer cell receptor genes leads to superior survival after unrelated transplantation for acute myelogenous leukemia. Blood (Plenary Paper), 2411-2419, 2010.
- Foley B, Cooley S, Verneris MR, Curtsinger J, Luo X, Waller EK, Anasetti C, Weisdorf D, Miller JS: 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, 2013.
- Romee R, Foley B, Lenvik T, Wang Y, Zhang B, Ankarlo D, Luo X, Cooley S, Verneris M, Walcheck, Miller JS: NK cell CD16 surface expression and function is regulated by a disintegrin and metalloprotease-17 (ADAM 17). Blood. 121(18): 3599-608, 2013.
- Wiernik A, Foley B, Zhang B, Verneris MR, Warlick E, Gleason MK, Ross JA, Luo X, Weisdorf DJ, Walcheck B, Vallera DA, Miller JS: 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, 2013.
- 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 JS: Recipient HLA-C1 enhances the clinical advantage of killer-cell immunoglobulin-like receptor B haplotype donors in unrelated transplantation for acute myelogenous leukemia. Journal of Immunology 15:192(10):4592-600, 2014.
- 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: CD16xCD33 bispecific killer cell engager (BiKE) activates NK cells from MDS patients against primary MDS and MDSC CD33+ target. Blood 123(19):3016-26, 2014.
- 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: Transient Regulatory T-cell (Treg) depletion with IL-2 Diphtheria Toxin fusion protein enhances clearance of acute myeloid leukemia by haploidentical natural killer (NK) cells Blood (Plenary Paper) 123(25):3855-63, 2014.