|
Ph.D. (1981)
University of California at Berkeley
|
David
J. Culp, Ph.D.
Associate
Professor of Pharmacology and Physiology in the Center for Oral
Biology
Primary
Appointment:
Pharmacology and Physiology
Center Affiliation:
Center for Oral Biology
GEBS Cluster Affiliations:
CMM-Cellular and Molecular
Basis of Medicine
|
Research:
Regulation
of exocrine cell secretion and gene expression |
Contact
Information:
E-mail: David_Culp@urmc.rochester.edu
|
University of Rochester
School of Medicine and Dentistry
601 Elmwood Ave, Box 711
Rochester, New York 14642
|
KMRB, G-9627
Phone: (585) 275-0402
Fax: (585) 276-0190 |
|
Research Overview
|
Our
laboratory is focused towards elucidation of signaling mechanisms
regulating exocrine secretion by glandular mucous cells. This
cell type is highly specialized to synthesize, package and secrete
high-molecular weight mucin glycoproteins which serve to protect
mucosal surfaces of the body, such as the oral cavity and the
respiratory and digestive tracts.
Mucous cells are tightly regulated by multiple neurotransmitters
to directly activate or inhibit cell secretion. Using rat sublingual
salivary glands as our mucous cell model we have determined
that exocrine secretion is elicited primarily by acetylcholine
and VIP (vasoactive intestinal peptide). Acetylcholine activates
secretion through m1 and m3 receptor subtypes mediated through
Gq/11 G-proteins and a Ca++ signaling pathway, whereas
receptors to VIP initiate a cAMP cascade. Simultaneous activation
of VIP and muscarinic receptors results in a synergistic secretion
mediated through a cAMP-dependent mechanism to release Ca++
from intracellular stores. Current studies are concerned with
elucidation of this cAMP-dependent Ca++ release mechanism
and understanding how persistent challenge with agonist regulates
m1 and m3 receptor function and expression.
These studies will provide specific information for the determination
of the dose and the temporal administration of agonist in future
clinical trials to treat patients with salivary hypofunction,
such as those suffering from auto-immune disease or recovering
from head and neck radiation therapy. We also have preliminary
evidence that muscarinic receptor activation is required to
maintain the mucous cell phenotype. We therefore are beginning
to explore mechanisms by which muscarinic receptor activation
controls mucous cell-specific gene expression. |
|
Recent Publications
|
| Click
 to
see publications by Dr. Culp indexed in the National Library
of Medicine's PubMed database.
|
Back
to Pharmacology and Physiology
Back to Center
for Oral Biology
|
