Research Interests Lyme disease, a global public health concern, has been reported in Europe, Asia, and North America. Reported cases of Lyme disease in the U.S. alone have been on the rise for over 10 years, with over 17,000 cases in the U.S. alone reported in 2000, making it the leading reportable arthropod-borne infectious disease. Lyme disease, caused by the bacterium Borrelia burgdorferi, is a multi-systemic disorder affecting the skin, heart, central nervous system, and joints. The disease generally occurs in two stages, early (acute) and late (chronic). Upon infection by the bite of an Ixodes tick, the spirochetes spread locally under the skin, often resulting in the formation of a migrating bull’s eye rash, termed erythema migrans (EM). EM is often accompanied by fever, headache, fatigue, arthralgia, myalgia, and neck/back pain. If the disease goes untreated or is misdiagnosed, the bacterium can invade deep tissue ranging from the heart to the brain, and can eventually lead to severe chronic arthritis. B. burgdorferi is a gram negative type bacterium that has a cellular envelope consisting of an inner membrane, a periplasmic space, and an outer membrane. Protected from the host immune system and housed between the inner and outer membranes are the flagella, termed endoflagella because of their location. The endoflagella give the spirochetes their unique shape (spiral) and allow the bacterium to move through viscous fluids (viscotaxis). The B. burgdorferi genome has been sequenced and consists of at least 22 different plasmids (circular and linear) and a linear chromosome. This unusual genome architecture has been a factor in hindering genetic manipulation of this bacterium, but recent advances in spirochete genetics have allowed for production of numerous B. burgdorferi mutants for study. We are interested in deciphering the molecular mechanisms that are involved in the adaptive response (changes in gene expression and protein synthesis) as the bacterium is transmitted from the tick vector to the mammalian host. Our primary focus is to elucidate the regulatory networks responsible for the differential gene expression observed when the spirochetes are shifted from pH 8.0/23oC (mimicking conditions of an unfed tick) to pH 7.0/33oC (mimicking conditions of a fed tick or mammalian host). Many of the genes that are expressed at pH 7.0/33oC verses pH 8.0/23oC are putative virulence determinants, and the study of their regulation is important in understanding how this bacterium is able to infect mammals and evade the host immune system.   Selected Publications Hughes JL, Nolder CL, Nowalk AJ, Clifton DR, Howison RR, Schmit VL, Gilmore RD Jr, Carroll JA. Borrelia burgdorferi surface-localized proteins expressed during persistent murine infection are conserved among diverse Borrelia spp. Infect Immun. 2008 Jun;76(6):2498-511. von Lackum K, Ollison KM, Bykowski T, Nowalk AJ, Hughes JL, Carroll JA, Zuckert WR, Stevenson B. Regulated synthesis of the Borrelia burgdorferi inner-membrane lipoprotein IpLA7 (P22, P22-A) during the Lyme disease spirochaete's mammal-tick infectious cycle. Microbiology. 2007 May;153(Pt 5):1361-71. Gilmore RD Jr, Howison RR, Schmit VL, Nowalk AJ, Clifton DR, Nolder C, Hughes JL, Carroll JA. Temporal expression analysis of the Borrelia burgdorferi paralogous gene family 54 genes BBA64, BBA65, and BBA66 during persistent infection in mice. Infect Immun. 2007 Jun;75(6):2753-64. Clifton, D.R., C.L. Nolder, J.L. Hughes, A.J. Nowalk, and J.A. Carroll. 2006. Regulation and expression of bba66 encoding an immunogenic infection-associated lipoprotein in Borrelia burgdorferi. Mol. Microbiol. Nowalk A.J., R.D. Gilmore, Jr., J.A. Carroll. 2006. Serologic proteome analysis (SERPA) of immunoreactive membrane-associated proteins of Borrelia burgdorferi expressed during mammalian infection. Infect Immun. 2006 Jul;74(7):3864-73. Complete Publication Listing   Grant Support Analysis of pgf 54 members in Lyme disease serodiagnosis. 2004 - 2008   Other Links University of Pittsburgh

James A Carroll, Ph.D. Office:  W1145 BST Lab:W1113 BST Phone:412-383-7696 jcarroll@mgb.pitt.edu   Academic Affiliations Department of Microbiology and Molecular Genetics (Primary Appointment)   Education 1990 B.S. Microbiology Clemson University Clemson, SC 1997 Ph.D. Microbiology University of Georgia Athens, GA 1997 - 2002 Postdoctoral Fellow Rocky Mountain Laboratory NIAID, NIH Hamilton, MT   Lab Personnel Technician: Christi Nolder Research Fellow: Andy Nowalk M.D., Ph.D. Research Associate: Dawn Clifton, Ph.D. Graduate Student: Jessica Hughes Lab phone: 412-383-8099