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Alan S. Cross

Alan S. Cross M.D.

Academic Title: Clinical Professor
Primary Appointment: Medicine
Location: HSF1, Room 480
Phone: (410) 706-5328
Phone: (410) 706-6499
Fax: (410) 706-6205

Personal History:

Dr. Cross is Professor of Medicine in the Division of Geographic Medicine and is Associate Director for Adjuvant Biology Research at the Center for Vaccine Development where he also is Chief of the Innate Immunity and Adjuvants Section. Dr. Cross is a graduate of Harvard College (1966) and the University of Pennsylavania School of Medicine (1970). Following training in internal medicine(Rush-Presbyterian-St. Luke's and Harvard medical Service, boston City Hospital) and infectious diseases (Strong memorial Hospital, Rochester, NY) , Dr. Cross entered active duty in the U.S. Army at the Walter Reed Army Institute of Research where he remained for twenty years (1974-1994). He developed vaccines for Gram-negative bacteria (Pseudomonas aeruginosa, Klebsiella and E. coli) as well as immune globulin enriched in antibodies against Pseudomonas and Klebsiella. Each of the vaccines progressed through phase I studies. Dr. Cross became Chief of the Department of Bacterial Diseases where he directed clinical studies on meningococcal and gonococcal infections as well as research on biodefense. After his retirement from the Army in 1994, he became Director of the Program in Infectious Diseases at the University of Maryland Greenebaum Cancer Center and member of the attending staff of the Division of Infectious Diseases. In 2003 he joined the Center for Vaccine Development where he is Chief of the Section on Adjuvant Biology and Innate Immunity Dr. Cross directed the Infectious Diseases Fellowship Program at the University of Maryland for two years, has served two rotations on the Anti-infective Drug Advisory Committee of the FDA, numerous ad hoc study sections for the NIAID and Department of Defense, an advisory committee for meningococcal vaccines at the Walter Reed Army Institute of Research and on many data safety and monitoring committees for clinical studies sponsored by industry and the NIH. In 2010 he served on a committee of the National Academy of Sciences that examined the Special Immunizations Program for Biodefense, a program that has provided vaccines for laboratory workers. He has been a program coordinator for the Middle Atlantic Regional Centers for Excellence in Biodefense and Emerging Infections. A recent president of the International Endotoxin and Innate Immunity Society, Dr. Cross was elected Fellow of the American Academy of Microbiology in 2010. Dr. Cross has authored 186 peer-reviewed papers, 221 abstracts, 44 book chapters and has been issued 8 patents for his discoveries.

Research Interests:

Dr. Cross has three major areas of interest: the development of a vaccine for the prevention and treatment of sepsis; novel interventions for biodefense and the role of sialic acid in the regulation of innate and adaptive immunity. A previous phase I study with a detoxified endotoxin vaccine complexed to group B meningococcal outer membrane protein revealed that while the vaccine was well-tolerated, it was only weakly immunogenic. Currently, preclinical studies in murine models as well as clinical studies in human subjects are continuing with this vaccine given in conjunction with novel adjuvants. The vaccine has been used to prepare bovine colostrum enriched in anti-endotoxin antibodies for use in "leaky gut" syndromes. In addition to developing vaccines against biodefense and emerging infectious agents, Dr. Cross is studying how peptides that antagonize co-stimulatory pathways may ameliorate viral and bacterial infections. Finally, his laboratory found that the sialidase (neuraminidase) activity of various host cells in the immune system is an essential element of innate and adaptive immunity. Currently the laboratory is focusing on the mechanisms by which human neutrophil sialidase regulates cellular trafficking in both in vivo and in vitro model systems. These studies rely on endothelial cell culture systems as well as murine models of inflammation, including acute lung injury.

Clinical Speciality:

Infectious diseases

Lab Techniques and Equipment:

Animal models of infection; glycobiology techniques


Kang, TJ, Basu,S, Zhang, L, Thomas, K, Vogel, S, Baillie L, Cross, A. B. anthracis spores and lethal toxin induce IL-1beta via functionally distinct signaling pathways. Eur J Immunol 2008;38:1574-84 (Featured article). PMID: 18493980

Li XL, Ezelle HJ, Kang TJ, Zhang L, Shirey KA, Harro J, Hasday JD, Mohapatra SK, Crasta OR, Vogel SN, Cross AS, Hassel BA. An essential role for the antiviral endoribonuclease, RNase-L, in antibacterial immunity. PNAS 2008;105:20816-21. PMID: 19075243

Chen WH, Toapanta FR, Shirey KA, Zhang L, Giannelou A, Page C, Frieman MB, Vogel S, Cross AS. Potential role for alternatively activated macrophages in the secondary bacterial infection during recovery from influenza. Immunology Letts 2012;141:227-34. Epub 2011 Oct 20 PMID 22037624

Lillehoj EP, Hyun SW, Feng C, Zhang L, Liu A, Guang W, Nguyen C, Luzina IG, Atamas SP, Passaniti A, Twadell WS, Puche AC, Wang L-X, Cross AS, Goldblum SE. NEU1 sialidase expressed in human airway epithelia regulates epidermal growth factor receptor (EGFR) and MUC1 signaling. J Biol Chem 2012;287:8214-31.

Feng C, Stamatos NM, Dragan A, Medvedev A, Whitford M, Zhang L, Song C, Rallabhandi P, Nhu Q, Vogel SN, Geddes C, Cross AS. Sialyl residues modulate LPS-mediated signaling through the Toll-like receptor 4 complex. PLoSOne 2012;7:e32359

Feng C, Zhang L, Almulki L, Faez S, Whitford M, Hafezi-Moghadam A, Cross AS. Endogenous PMN sialidase activity exposes activation epitope on CD11b/CD18 which enhances its binding interaction with ICAM-1. J. Leukoc. Biol. 2011;90:313-321

Cross AS, Hyun SW, Miranda-Ribera A, Feng C, Liu A, Nguyen C, Zhang L, Luzina IG, Atamas SP, Twaddell WS, Guang W, Lillehoj EP, Puché AC, Huang W, Wang L-X, Passaniti A, and Goldblum SE. NEU1 and NEU3 sialidase activity expressed in human lung microvascular endothelia. NEU1 restrains endothelial cell migration whereas NEU3 does not. J Biolog Chem 2012;287:15966-80.

Chen WH, Toapanta FR, Shirey KA, Zhang L, Giannelou A, Page C, Frieman MB, Vogel S, Cross AS. Potential role for alternatively activated macrophages in the secondary bacterial infection during recovery from influenza. Immunology Letts 2012;141:227-34. Epub 2011 Oct 20 PMID 22037624

Cross AS, Development of an anti-endotoxin vaccine for sepsis. In: Endotoxins: Structure, function and recognition, X. Wang and P. Quinn, editors. Subcellular Biochemistry 2010; 53:285-302, Springer

Chen WH, Kang TJ, Bhattacharjee AK, Cross AS. Intranasal administration of detoxified endotoxin vaccine protects mice against heterologous Gram-negative bacterial infection. Innate Immunity 2008;14:269-278.

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.

Cross AS, Opal SM, Palardy JE, Drabick JJ, Warren HS, Huber C, Cook P, Bhattacharjee AK. Phase I study of detoxified Escherichia coli J5 lipopolysaccharide/group B meningococcal outer membrane protein complex vaccine to human subjects. Vaccine, 2003;21:4576-4587.

Ramachandran G, Tulapurkar ME2, Harris KM, Arad G, Shirvan A, Shemesh R, DeTolla LJ, Benazzi C, Opal SM, Kaempfer R, Cross AS. A peptide antagonist of CD28 signaling attenuates toxic shock and necrotizing soft tissue infection induced by Streptococcus pyogenes J. Infect Dis. 2013 (in press)