Research Areas

Current research interests in Dr. Merchant's laboratory concern the molecular mechanisms underlying normal and neoplastic epithelial cell growth in the luminal gastrointestinal (GI) tract. The GI tract abundantly expresses growth factors, many of which bind and activate the EGF receptor present on mucosal cells. Dr. Merchant's lab has cloned a zinc finger protein (ZBP-89) that binds to a GC-rich DNA element in the gastrin promoter and confers EGF responsiveness. The full-length protein functions as a repressor of growth factor signals regulating the gastrin promoter. Several other growth related promoters are also regulated by ZBP-89. The lab recently completed studies which indicate that ZBP-89 regulates growth in part by stimulating the cyclin-dependent kinase inhibitor, p21waf1, in a butyrate-dependent manner through recruitment of the histone acetyl transferase p300. Moreover, ZBP-89 triggers growth arrest in a p53-dependent manner by preventing nuclear export of p53. ZBP-89 also induces apoptosis, but this process occurs independent of p53. Thus ZBP-89 is likely involved in growth regulation and cancer.

Helicobacter pylori is the major cause of duodenal ulcers and gastric cancer. The organism does not invade the mucosa, rather it triggers acute and chronic inflammation as well as gastric atrophy of the gastric mucosa. Subsequently, serum gastrin levels increase and intestinal metaplasia and cancer may develop. Our recent studies this year involve the use of animal and cell culture models to dissect the pathways by which bacterial colonization leads to ulcer development and subsequently cancer. Ongoing projects in the laboratory have revealed that outer membrane proteins stimulate the gastrin and interleukin-8 promoters and may be a general mechanism by which bacterial proteins activate mammalian cell signaling pathways and gene expression. In particular, her lab has recently found that bacterial overgrowth and specific cytokines mimic the pathology observed with Helicobacter pylori infection in mice, suggesting that chronic atrophic gastritis is not a host response specific to this organism, but is the general response of the stomach to bacterial colonization.

The transcriptional control of gastrin occurs in two settings, in the stomach, when gastrin gene expression is activated by pH or inflammation, and in cancer, when genes that normally suppress (e.g., menin in ZE) or activate (e.g. ras in colon cancer) transcription are mutated resulting in aberrant overexpression. Prior studies in my lab have focused on identifying regulatory elements that mediate inducible regulation of the gastrin promoter, identifying the transacting factors that bind these elements and studying the signal transduction pathways that target these transcription factors. Several DNA elements appear to mediate basal, inducible and tissue specific regulation of the gastrin promoter. Only three families of transcription factors have been reported to bind to most of these elements. Dr. Merchant's lab has contributed significantly to studies directed towards understanding how these two zinc finger transcription factor families, Sp1 and ZBP-89, regulate the gastrin promoter. Current studies involve studying how the DNA elements identified in cell lines mediate expression of the gastrin gene in vivo.

Study Projects

• Bacterial colonization and chronic inflammatory changes in the stomach
• Regulatory networks controlling acid secretion and homeostatis
• ZBP-89 and control of cell growth

Selected Publications

Please click here to see a list of publications by Dr. Merchant.

Honors/Awards

• Damon Runyon-Walter Winchell Research Award, Stanford
• Honors and Distinction in Biological Sciences, Stanford
• Henry J. Kaiser Award, Yale School of Medicine
• Alpha Omega Alpha, Yale School of Medicine
• Medical Scientist Award, Yale School of Medicine
• Robert Wood Johnson Minority Faculty Development Award
• Munn Endowment Cancer Award, University of Michigan
• University of Michigan, Faculty Career Development Award
• Robert and Sally Funderburg Award for Gastric CancerMember, American Society for Clinical Investigation
• Jerome W. Conn Award for Distinguished Research by a Junior Faculty Member in Internal Medicine

Professional Memberships

• Gastroenterology Research Group
• American Society for Microbiology
• American Gastroenterological Association
• American Federation of Clinical Research
• Midwest Gut Club
• Central Society for Clinical Research
• American Association for Cancer Research
• American Society for Biochemistry and Molecular Biology
• American Society for Clinical Investigation

Academic Information

Office address:
2051 BSRB
109 Zina Pitcher Place, SPC 2200
Ann Arbor, MI 48109
Tel: 734-647-2944
Fax: 734-763-4686