Jeffrey Miller, M.D.

Jeffrey Miller, M.D. is a Professor of Medicine, Director of the University of Minnesota Cancer Center Cell Therapy Core Laboratory, and Medical Director of the Inpatient Adult Bone Marrow Transplant Unit at Fairview-University Medical Center, Minneapolis.

Dr. Miller received a bachelor of science degree from Northwestern University in Evanston, Ill., and a medical degree 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, he joined the faculty in 1991.

Dr. Miller's research team works in two areas that seek to understand fundamental issues regarding innate immune function: 1.) How undifferentiated stem cells develop into functioning NK cell lymphocytes, and 2.) How to manipulate NK cells to treat or prevent cancer relapse. A major emphasis is on natural killer (NK) cell development. Recently, receptors on NK cells have been identified that recognize class I MHC molecules. The hypothesis underlying current research efforts is that "self" MHC molecules influence the NK cell receptor repertoire during development. Laboratory evaluation and human clinical trials will test the hypothesis that a mismatch between NK receptor and class I alleles on recipient tumor will result in greater tumor kill.

The second major emphasis in Dr. Miller’s laboratory is based on pre-clinical and clinical studies to develop effective anti-tumor immunotherapies.  Early studies focused on nonspecific immune stimulation using subcutaneous IL-2.  Strong evidence suggests that this nonspecific therapy alone will be ineffective and current efforts aim to target effectors specifically to tumor cells.  For natural killer cells, current approaches include combined therapy with monoclonal antibodies and interleukin-2 to target therapy through antibody dependent cellular cytotoxicity (ADCC).  To target T-cells, we have initiated studies using cancer vaccines.

Selected Publications

Miller JS, McCullar V, Punzel M, Lemischka IR,  Moore KA.  Single adult human CD34+/Lin-/CD38- progenitors give rise to NK cells, B-lineage cells, dendritic cells and myeloid cells.  Blood 1999; 93:  96-106.

Miller JS, Cervenka T, Lund J, Okazaki IJ, Moss J. Purine metabolites suppress proliferation of human natural killer cells through a lineage specific P2 purine receptor.  J Immunology 1999; 162:  7376-7382.

Cooley S, Burns LJ, Miller JS:  Natural killer cell cytotoxicity of breast cancer targets is enhanced by two distinct mechanisms of antibody dependent cellular cytotoxicity against LFA-3 and HER2/neu.  Experimental Hematology 1999; 27:  1533-1541.

Lickliter JD, Kratzke RA, Nguyen FL, Niehans GA, Miller JS:  Fas ligand is highly expressed in acute leukemia and during the transformation of chronic myeloid leukemia to blast crisis.  Experimental Hematology 1999; 27:  1519-1527.

Burns LJ, Weisdorf DJ, DeFor TE, Repka TL, Ogle KM, Hummer C, Miller JS:  Enhancement of the anti-tumor activity of a peripheral blood progenitor cell graft by mobilization with IL-2 plus G-CSF in patients with advanced breast cancer.  Experimental Hematology 2000; 28:  96-103.

Toor AA, Lund TC, Miller JS.  T-Cell Factor-1 (TCF-1) Expression During Human NK Cell Development and in Circulating CD56+bright NK Cells.  Exp Hematology 2001; 29:  499-506.

Miller JS, McCullar V.  Human NK cells with polyclonal lectin and immunoglobulin receptors develop from single hemtopoietic stem cells with preferential expression of NKG2A and KIR2DL2/L3/S2.  Blood 2001; 98:705-713..

Miller JS.  The biology of natural killer cells in cancer, infection and pregnancy.  Exp Hem 2001; 29:1157-68.

Davies SM, DeFor TE, McGlave PB, Miller JS, Verfaillie CM, Wagner JE, Weisdorf DJ.  Equivalent outcomes in patients with chronic myelogenous leukemia after early transplantation of phenotypically matched bone marrow from related or unrelated donors.  Am J Med 2001; 110:339-46.

Chiorean EG, Miller JS.  The biology of natural killer cells and implications for therapy of human disease. J Hematother & Stem Cell Res 2001; 10:451-63.

Nakajima H, Zhao R, Ward J, Dolan M, Hirsch B, Miller JS:  The BCR/ABL transgene causes abnormal NK cell differentiation and can be found in circulating NK cells of advanced phase CML patients. J. Immunology 2002; 168:643-650.

Orchard PJ, Blazar BR, Burger S, Levine B, Basso L, Nelson DM, Gordon K, McIvor RS, Wagner JE, Miller JS.  Clinical-scale selection oa anti-CD3/CD28-activated T cells after transduction with a retroviral vector expressing herpes simplex virus thymidine kinase and truncated nerve growth factor receptor.  Human Gene Therapy 2002; 13:979-88.

Davies SM, Ruggieri L, Defor T, Wagner JE, Weisdorf DJ, Miller JS, Velardi A, Blazar BR: Evaluation of KIR ligand incompatibility in mismatched unrelated donor hematopoietic transplants.  Blood 2002; 100:3825-27.

Barker JN, Davies SM, DeFor TE, Burns LJ, McGlave PB, Miller JS, Weisdaorf DJ.  Determinants of survival after human leukocyte antigen-matched unrelated donor bone marrow transplantation in adults.  British J. Haematology 2002; 118:101-7.

Feltis BA. Miller JS. Sahar DA. Kim AS. Saltzman DA. Leonard AS. Wells CL. Sielaff TD. Liver and circulating NK1.1(+)CD3(-) cells are increased in infection with attenuated Salmonella typhimurium and are associated with reduced tumor in murine liver cancer. Journal of Surgical Research 2002; 107:101-7.

Burns LJ, Weisdorf DW, Vesole D, Repka T, Blazar BR, Burger SR, Panoskalysis-Mortari A, Keever-Taylor CA, Zhang MJ, Miller JS:  IL-2 Based Immunotherapy after Autologous Transplantation for Lymphoma and Breast Cancer Induces Immune Activation and Cytokine Release: A Phase I/II Trial. Bone Marrow Transplantation 2003; 32:177-186.

Sachdev, D, Li, S, Hartell, JS, Fujita-Yamaguchi, Y, Miller, JS, and Yee, D.  A chimeric single-chain antibody against the type I insulin-like growth factor receptor renders breast cancer cells refractory to the mitogenic effects of IGF-I.  Cancer Research 2003; 63:627-635.

Chiorean EG, Dylla, SJ, Olsen K, Dylla S, Lenvik T, Miller JS:  BCR/ABL Alters the Function of NK Cells and the Acquisition of Killer Immunoglobulin-like Receptors (KIR). Blood 2003; 101:3527-33.

Barker JN, Weisdorf DJ, DeFor TE, Blazar BR, Miller JS, Wagner JE.  Rapid and complete donor chimerism in adult recipients of unrelated donor umbilical cord blood transplantation after reduced-intensity conditioning.  Blood 2003; 102:1915-9.

Chiorean EG, DeFor TE, Weisdorf DJ, Blazar BR , McGlave PB, Burns LJ, Charlotte Brown C, Miller JS: Donor Chimerism does not Predict Response to DLI for Relapsed CML after Allogeneic Hematopoietic Cell Transplantation, Biology of Blood and Marrow Transplantation 2004; 10:171-77.

Chen W, Chan ASH,  Dawson AJ, Liang X,  Blazar BR,  Miller JS: FLT3-ligand administration after hematopoietic cell transplantation increases circulating dendritic cell precursors that can be activated by CpG oligodeoxynucleotides to enhance T-cell and NK-cell function. Biology of Blood and Marrow Transplantation 2005; 11:23-34.