Department:
Medicine, Center for Vaccine Development
UMGCC Research Program:
Experimental Therapeutics Program Tumor Immunology and Immunotherapy
Education/Training:
College Degree:
B.A., Harvard College
Medical Degree:
M.D., University of Pennsylvania
Residency:
Internal Medicine, Rush-Presbyterian St. Luke's Medical Center
Harvard Medical Service, Boston City Hospital
Fellowship:
Infectious Diseases, Strong Memorial Hospital, Rochester, NY
Walter Reed Army Institute of Research
Certification:
Internal Medicine; Infectious Diseases
Contact
Information:
Mailing Address:
Center for Vaccine Development
HSF I, Suite 480
685 W. Baltimore Street
Baltimore, MD 21201
Email:
across@umm.edu
Phone:
410-706-5328
Fax:
410-706-6205
Research Interests:
I am interested in innate immunity, particularly as it relates to host defenses against bacterial infections. My laboratory has defined the role of sialic acid modulation on host responses to inflammatory stimuli. Sialidases of cells in the immune system remove sialyl acid residues from the surface of cells. This enhances cellular responsiveness to activating stimuli, increases cell adhesion to and migration across the endothelium and modifies the activity of surface adhesion moleucles. Moreover, we found that the HIV "pirates" the lymphocyte sialidase to facilitate invasion of that cell. Sialyltransferases put sialyl residues back onto the cell and return the cell to its basal state. Thus the removal and addition of sialyl residues constitutes a new regulatory system that governs the responsiveness of cells of the immune system.
We are also interested in immune reconstitution and vaccine development. In conjunction with Drs. Rapoport and Mann, and in collaboration with investigators at the University of Pennsylvania, we established a platform which we hope will allow future studies of cancer vaccines. Using a pneumococcal conjugate vaccine for proof of principle, we showed that patients undergoing autologous stem cell transplantation can respond optimally to a vaccine antiggen if the patients are immunized before lymphocyte and stem cell harvest. After ex vivo co-stimulation of the lymphocytes, patients respond better to vaccine antigens if they receive the co-stimulated lymphocytes before the vaccine. We now plan to extend this strategy to other antimicrobial vaccines and to cancer vaccines.
Finally, we have developed a vaccine against sepsis that has been tested in phase I trials in human subjects. This vaccine may be useful in the stem cell transplant setting where endotoxin may play a role in graft rejection.
Publications:
Roghmann M, Taylor KL, Gupta A, Zhan M, Johnson JA, Cross A, Edelman R and Fattom A. Epidemiology of capsular and surface polysaccharide in S. aureus infections complicated by bacteremia. J. Hosp Infect. 2005;59:27-32.
Opal SM, Palardy JE, Chen WH, Parejo NA, Bhattacharjee AK, Cross AS. Active immunization with a detoxified endotoxin vaccine protects against lethal polymicrobial sepsis: its use with CpG adjuvant and potential mechanisms. J. Infect. Dis 2005;192:2074-2080.
Jain M, Titanji R, Rapoport AP, Wang W, Gocke C, Cross A, Akpek G. A fatal Clostridium infection in an allogeneic stem cell transplant recipient. Bone Marrow Transplantation 2005, 1-3.
Kang TJ, Fenton MJ, Weiner MA, Hibbs S, Basu S, Baillie L, Cross AS. Murine macrophages kill the vegetative form of Bacillus anthracis. Infect Immun 2005; 73:7495-7501.
Dinits-Pensy M, Forrest G, Cross AS, Hise M. The use of vaccines in adult patients` with renal disease. American J. Kidney Diseases 2005;46:997-1011
Rapoport AP*, Stadtmauer EA*, Aqui N*, Badros A, Cotte J, Chrisley L, Veloso E, Zheng Z, Westphal S, Mair S, Chi N, Ratterree B, Pochran MF, Natt S, Hinkle J, Sickles C, Sohal A, Ruehle K, Lynch C, Zhang L, Porter DL, Luger S, Guo C, Fang H-B, Blackwelder W, Hankey K, Mann D, Edelman R, Frasch C, Levine BL*, Cross A*, June CH*. Restoration of immunity in lymphopenic cancer patients by combination vaccination and adoptive T cell transfer. Nature Medicine 2005;11:1230-7. (* equal contributors)
McNeely T, Luo S, Manger W, Herber W, Schofield T, Tan C, Newman K, Sadoff J, Donnelly J, Cross A. Development of an opsonin inhibition assay for evaluation of complex polysaccharide protective epitopes. Vaccine, 2005(in press).
