Dr. Mullen serves as the Chief of the Pediatric Hematology / Oncology Division. He is also the Director the Fellowship Program, and leads the Experimental Hematology Program at the University of Rochester. He has joint appointments as Professor in both the Department of Microbiology and Immunology and Professor in the Department of Oncology.
Dr. Mullen's research interests are: Cancer Immunobiology and Transplant Immunology.
The goal of Dr. Mullen's research is to use murine models of allogeneic hematopoietic stem cell (HSC) transplantation to identify immunological mechanisms that can be used to design therapies that will reduce the likelihood of leukemia relapse after allogeneic HCS transplant in children with leukemia. In allogeneic HSC transplant the graft versus leukemia (GVL) effect is closely associated with GVHD and clinical attempts to separate the two have not been successful. In the absence of specific immune manipulation the dominant allogeneic immune response that develops after transplant is directed at immunodominant, widely distributed host antigens, and the post-transplant environment does not favor development of immune responses with relative selectively for antigens on minimal residual leukemia.
His laboratory has recently demonstrated that allogeneic HSC transplant recipients treated after transplant with cellular tumor vaccines exhibit prolonged survival but do not experience exacerbations of GVHD. The mechanism of this vaccine effect is under investigation. The central hypothesis in this work is that post-transplant tumor vaccines can enhance systemic immune responses that can control minimal residual leukemia without exacerbation of clinically significant graft versus host disease.
Active projects in the lab include the following:
1)Testing the hypothesis that after allogeneic hematopoietic stem cell transplantation moderate affinity T cells specific for subdominant minor histocompatibility antigens can be activated by vaccines to exert antileukemia activity without GVHD.
2) Testing the hypothesis that allogeneic delayed lymphocyte infusion for acute lymphoblastic malignancies can be made more effective by simultaneous vaccination against leukemia associated antigens.
3) To identify the leukemia associated antigenic targets of T cells induced by post-transplant tumor vaccines and to determine if these empirically identified genes correlate with classes of genes predicted to be antigenic based on gene expression analysis.
Hsu YC, Mildenstein K, Hunter K, Tkachenko O, Mullen CA. "Acute lymphoid leukemia cells with greater stem cell antigen-1 (Ly6a/Sca-1) expression exhibit higher levels of metalloproteinase activity and are more aggressive in vivo." PloS one. 2014 9(2):e88966. Epub 2014 Feb 20.
Oyeku SO, Driscoll MC, Cohen HW, Trachtman R, Pashankar F, Mullen C, Giardina PJ, Velazco N, Racine AD, Green NS. "Parental and other factors associated with hydroxyurea use for pediatric sickle cell disease." Pediatric blood & cancer. 2013 Apr; 60(4):653-8. Epub 2012 Nov 05.
Green NS, Ender KL, Pashankar F, Driscoll C, Giardina PJ, Mullen CA, Clark LN, Manwani D, Crotty J, Kisselev S, Neville KA, Hoppe C, Barral S. "Candidate sequence variants and fetal hemoglobin in children with sickle cell disease treated with hydroxyurea." PloS one. 2013 8(2):e55709. Epub 2013 Feb 07.
Milner LA, Becker MW, Bernstein SH, Bruckner L, Friedberg JW, Holland GA, Ifthikharuddin JJ, Liesveld JL, Mathes EJ, Menchel HL, Mullen CA, Sasson T, Phillips GL. "Intra-arterial methylprednisolone for the management of steroid-refractory acute gastrointestinal and hepatic graft versus host disease." American journal of hematology. 2011 Aug; 86(8):712-4. Epub 2011 May 31.
Jansson J, Hsu YC, Kuzin II, Campbell A, Mullen CA. "Acute lymphoblastic leukemia cells that survive combination chemotherapy in vivo remain sensitive to allogeneic immune effects." Leukemia research. 2011 Jun; 35(6):800-7. Epub 2010 Nov 12.