James F. Battey, M.D., Ph.D.

Director, NIDCD

Senior Investigator
G-protein Coupled Receptors' Section, NINDS

Research Statement

The G-protein Coupled Receptors' Section is interested in elucidating the structure, function, and regulation of the largest family of proteins in the genome that mediate intracellular signaling. Our attention is focused primarily on the bombesin receptor subfamily and candidate taste receptors.

Bombesin Receptor Family: Mammalian bombesin receptors mediate a wide spectrun of physiologic processes, including hormone release, smooth muscle contraction, and cell division. There are three different bombesin receptors with distinct structural and pharmacologic properties: the gastrin-releasing peptide receptor, the neuromedin B receptor, and bombesin receptor subtype 3. We have used site-directed mutagenesis to define structural motifs critical for ligand binding, G protein coupling, and receptor activity. At the present time, we are using gene targeting strategies to determine the function of each receptor in the context of an intact mouse. In addition, we are exploring the role of phosphorylation and additional receptor binding proteins in regulating receptor activity.

Taste Receptors: We are collaborating with Dr. Susan Sullivan's laboratory in creating a cDNA library enriched for cDNAs from transcripts selectively expressed in taste cells. About 20,000 clones from this library will be sequenced in an effort to identify novel molecules (receptors, G protein subunits, effectors, channels, etc.) that are selectively expressed in taste receptor cells. Candidate molecules will be assessed for their importance in mediating sense of taste.

Lab Personnel

Lori L Hampton (Send e-mail)
Glenn Kroog, MD (Send e-mail)
Eduardo Sainz (Send e-mail)
Dan Xi, Ph.D. (Send e-mail)
Jian Xiaoying, Ph.D. (Send e-mail)

Selected Publications

• Austin CP, Battey JF, Bradley A, Bucan M, Capecchi M, Collins FS, Dove WF, Duyk G, Dymecki S, Eppig JT, Grieder FB, Heintz N, Hicks G, Insel TR, Joyner A, Koller BH, Lloyd KC, Magnuson T, Moore MW, Nagy A, Pollock JD, Roses AD, Sands AT, Seed B, Skarnes WC, Snoddy J, Soriano P, Stewart DJ, Stewart F, Stillman B, Varmus H, Varticovski L, Verma IM, Vogt TF, von Melchner H, Witkowski J, Woychik RP, Wurst W, Yancopoulos GD, Young SG, Zambrowicz B. The knockout mouse project. Nature Genetics 36(9):921–4, 2004.
• Naz S, Griffith AJ, Riazuddin S, Hampton LL, Battey JF Jr, Khan SN, Riazuddin S, Wilcox ER, Friedman TB. Mutations of ESPN cause autosomal recessive deafness and vestibular dysfunction. Journal of Medical Genetics 41(8):591–5, 2004.
• Insel TR, Volkow ND, Landis SC, Li TK, Battey JF, Sieving P; National Institutes of Health. Limits to growth: why neuroscience needs large-scale science. Nature Neuroscience 7(5):426–7, 2004.
• Insel TR, Volkow ND, Li TK, Battey JF, Landis SC. Neuroscience Networks: Data-sharing in an Information Age. PLoS Biology 1(1):E17, 2003.
• Ally RA, Ives KL, Traube E, Eltounsi I, Chen PW, Cahill PJ, Battey JF, Hellmich MR, Kroog GS. Agonist- and protein kinase C-induced phosphorylation have similar functional consequences for gastrin-releasing peptide receptor signaling via Gq. Molecular Pharmacology 64(4):890–904, 2003.
• Battey JF Jr. Using genetics to understand auditory function and improve diagnosis. Ear and Hearing 24(4):266–9, 2003.
• Hampton LL, Wright CG, Alagramam KN, Battey JF, Noben-Trauth K. A new spontaneous mutation in the mouse Ames waltzer gene, Pcdh15. Hearing Research 180(1–2):67–75, 2003.
• Gu XX, Rudy SF, Chu C, McCullagh L, Kim HN, Chen J, Li J, Robbins JB, Van Waes C, Battey JF. Phase I study of a lipooligosaccharide-based conjugate vaccine against nontypeable Haemophilus influenzae. Vaccine 21(17–18):2107–14, 2003.
• Shumyatsky GP, Tsvetkov E, Malleret G, Vronskaya S, Hatton M, Hampton L, Battey JF, Dulac C, Kandel ER, Bolshakov VY. Identification of a signaling network in lateral nucleus of amygdala important for inhibiting memory specifically related to learned fear. Cell 111(6):905–18, 2002.
• Ladenheim EE, Hampton LL, Whitney AC, White WO, Battey JF, Moran TH. Disruptions in feeding and body weight control in gastrin-releasing peptide receptor deficient mice. The Journal of Endocrinology 174(2):273–81, 2002.
• Carroll RE, Matkowskyj K, Saunthararajah Y, Sekosan M, Battey JF, Benya RV. Contribution of gastrin-releasing peptide and its receptor to villus development in the murine and human gastrointestinal tract. Mechanisms of Development 113(2):121–30, 2002.
• Kurima K, Peters LM, Yang Y, Riazuddin S, Ahmed ZM, Naz S, Arnaud D, Drury S, Mo J, Makishima T, Ghosh M, Menon PS, Deshmukh D, Oddoux C, Ostrer H, Khan S, Riazuddin S, Deininger PL, Hampton LL, Sullivan SL, Battey JF Jr, Keats BJ, Wilcox ER, Friedman TB, Griffith AJ. Dominant and recessive deafness caused by mutations of a novel gene, TMC1, required for cochlear hair-cell function. Nature Genetics 30(3):277–84, 2002.
• Moldin SO, Farmer ME, Chin HR, Battey JF Jr. Trans-NIH neuroscience initiatives on mouse phenotyping and mutagenesis. Mammalian Genome 12(8):575–81, 2001.
• Battey JF Jr. News from the National Institute on Deafness and Other Communication Disorders. Otology & Neurotology 22(3):287–90, 2001.
• Sainz E, Korley JN, Battey JF, Sullivan SL. Identification of a novel member of the T1R family of putative taste receptors. Journal of Neurochemistry 77(3):896–903, 2001.
• Benya RV, Kusui T, Katsuno T, Tsuda T, Mantey SA, Battey JF, Jensen RT. Glycosylation of the gastrin-releasing peptide receptor and its effect on expression, G protein coupling, and receptor modulatory processes. Molecular Pharmacology 58(6):1490–501, 2000.
• Hu WG, Chen J, Battey JF, Gu XX. Enhancement of clearance of bacteria from murine lungs by immunization with detoxified lipooligosaccharide from Moraxella catarrhalis conjugated to proteins. Infection and Immunity 68(9):4980–5, 2000.
• Carroll RE, Matkowskyj KA, Tretiakova MS, Battey JF, Benya RV. Gastrin-releasing peptide is a mitogen and a morphogen in murine colon cancer. Cell Growth & Differentiation 11(7):385–93, 2000.
• Weber HC, Jensen RT, Battey JF. Molecular organization of the mouse gastrin-releasing peptide receptor gene and its promoter. Gene 244(1–2): 137–49, 2000.
• Battey JF. A genetic approach to understanding inner ear function. The Journal of Clinical Investigation 106(12):1431–2, 2000.
• Hoon MA, Adler E, Lindemeier J, Battey JF, Ryba NJ, Zuker CS. Putative mammalian taste receptors: a class of taste-specific GPCRs with distinct topographic selectivity. Cell 96(4):541–51, 1999.
• Donohue PJ, Sainz E, Akeson M, Kroog GS, Mantey SA, Battey JF, Jensen RT, Northup J. An aspartate residue at the extracellular boundary of TMII and an arginine residue in TMVII of the gastrin-releasing peptide receptor interact to facilitate heterotrimeric G protein coupling. Biochemistry 38(29):9366–72, 1999.
• Ryan RR, Katsuno T, Mantey SA, Pradhan TK, Weber HC, Coy DH, Battey JF, Jensen R. Comparative pharmacology of the nonpeptide neuromedin B receptor antagonist PD 168368. The Journal of Pharmacology and Experimental Therapeutics 290(3):1202–11, 1999.
• Kroog GS, Jian X, Chen L, Northup JK, Battey JF. Phosphorylation uncouples the gastrin-releasing peptide receptor from G(q). The Journal of Biological Chemistry 274(51):36700–6, 1999.
• Jian X, Sainz E, Clark WA, Jensen RT, Battey JF, Northup JK. The bombesin receptor subtypes have distinct G protein specificities. The Journal of Biological Chemistry 274(17):11573–81, 1999.
• Sainz E, Akeson M, Mantey SA, Jensen RT, Battey JF. Four amino acid residues are critical for high affinity binding of neuromedin B to the neuromedin B receptor. The Journal of Biological Chemistry 273(26):15927–32, 1998.
• Hampton LL, Ladenheim EE, Akeson M, Way JM, Weber HC, Sutliff VE, Jensen RT, Wine LJ, Arnheiter H, Battey JF. Loss of bombesin-induced feeding suppression in gastrin-releasing peptide receptor deficient mice. Proceedings of the National Academy of Sciences of the USA 95(6):3188–92, 1998.
• Akeson M, Sainz E, Mantey SA, Jensen RT, Battey JF. Identification of four amino acids in the gastrin-releasing peptide receptor that are required for high affinity agonist binding. The Journal of Biological Chemistry 272(28):17405–9, 1997.

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