Mae Ciancio, Ph.D.

Associate Professor


 Midwestern University
 College of Health Sciences
 Biomedical Sciences Program
 Chicago College of Osteopathic Medicine (Physiology)
 College of Dental Medicine-Illinois
 Science Hall 203-F
 555 31st St.
 Downers Grove, IL 60515
Office: (630) 515-6107
e-mail: mcianc@midwestern.edu

EDUCATION

Ph.D.    Physiology         Loyola University Chicago           1989
B.A.      Chemistry           Northwestern University              1981
 

RESEARCH SUMMARY

Major research interests

The overall research focus of my laboratory is to demonstrate and elucidate the protective effect of Heat Shock Protein 70 (Hsp70) against diet-induced obesity (DIO), Chlamydia muridarum infection, oral squamous cell carcinoma, and Salmonella typhimurium-induced gastroenteritis.  We utilize a novel heat shock protein 70 transgenic mouseline for these studies that specifically expresses Hsp70 in all mature epithelial cells.  As such, it provides a useful model for exploring the innate immunity and host protective properties of Hsp70.  Students in my laboratory work closely with me and my research assistant.  We are currently in the process of exploring cellular mechanisms responsible for the protective activities of Hsp70 in each of these areas of investigation.    


Research projects

Project I: Heat Shock Protein 70 Protects Against High Fat Diet-induced Obesity:  The Role of Tight Junctional Proteins and Cytokines  (Collaborators: Dr. Christian Evans and Dr. Kathy LePard)

Recent findings reported by our laboratory demonstrate that epithelial cell expression of Hsp70 protects mice from high fat diet-induced obesity [Glawe, et al.  Gastroenterology. 146(5):S-111-S-112, 2014].  More specifically, Hsp70 transgenic mice fed a high fat diet demonstrated less adiposity and improved glucose handling compared to their wild-type littermates without the transgene.  These findings have profound clinical application, for they suggest that the continuous production of the stress-inducible Hsp70 can prevent or limit the low grade systemic inflammation reported to be a major contributor to diet-induced obesity.  Our current studies are designed to determine the cellular mechanisms responsible for the obesity-prevention activities of Hsp70.


Project II: Heat Shock Protein 70 Significantly Reduces Ovarian Inflammation Associated with Chlamydia muridarum Infection (Collaborators:  Dr. Ash Murthy and Dr. Weidang Li)

Chlamydia trachomatis is the most common reported cause of sexually transmitted bacterial infections in the United States: over a million new cases are reported to the CDC annually in the United States.  While most women are asymptomatic, 40% of infected, untreated women with C. trachomatis will go on to develop pelvic inflammatory disease, and approximately 25% will develop infertility.  Our laboratory recently demonstrated that Hsp70 expression can significantly reduce the ovarian inflammation associated with chlamydia infection (Do, et al American Osteopathic Association Meeting, Fall, 2014).  The Hsp70 transgenic mice displayed significantly reduced incidence and severity of oviduct dilation, not uterine horn pathology, at 80 days post-infection when compared to their non-transgenic littermates.  These results suggest that epithelial cell-specific Hsp70 expression in the urogenital tract serves a protective function against oviduct pathology following chlamydial infection.

Project III: Does Heat Shock Protein 70 Protect Against 4NQO-induced Oral Squamous Cell Carcinoma?  (Collaborator:  Dr. Bruno Jham)

Oral cancer accounts for 2.5% of new cancer cases annually and 1.4% of cancer related deaths.  Smoking and alcohol consumption increase the incidence of developing oral cancer. Innate immune mechanisms that may prevent oral cancer development would significantly improve the lives of people at risk for developing this disease. Whether production of heat shock protein 70 in the oral epithelium or secreted into saliva could protect against the carcinogenic effects of 4NQO, a water soluble carcinogen reported to mimic the effects of tobacco, has not been explored.  The purpose of this project is to evaluate, specifically, the effect of heat shock protein 70 (Hsp70) in modulating the carcinogenic response to 4NQO in a murine model.  The findings from these studies will be used to develop a new area of research for students to explore in collaboration with CDMI faculty.

 Project IV: Does Hsp70 Provide Innate Host Defense against Salmonella Infection?

As evidenced by the continued outbreaks of Salmonella-related food poisoning, bacterial infection resulting from the oral consumption of contaminated foods is a significant health risk.  Discovering ways to enhance the innate immune response to protect against these types of infections would provide a unique health benefit to the global population.  Interestingly, most bacterial gastrointestinal pathogens invade in the small intestines, an area virtually void of Hsp70 levels under non-stressed conditions. Previous studies in my lab have demonstrated that induced expression of Hsp70 significantly reduces the amount of Salmonella attachment and invasion of intestinal epithelial cells using an in vitro cell culture model and ex vivo isolated intestinal loop model.  Further studies using the Hsp70 transgenic model are designed to evaluate the protective effect of Hsp70 in vivo.

Selected Publications (See PubMed results)

Evans CC, LePard KJ, Kwak JW, Stancukas MC, Laskowski S, Dougherty J, Moulton L, Glawe A, Wang Y, Leone V, Antonopoulos DA, Smith D, Chang EB, Ciancio, MJ. Exercise prevents weight gain and alters the gut microbiota in a mouse model of high fat diet-induced obesity. PLoS One.  9(3):e92193, 2014. PMID: 24670791; PMCID: PMC3966766

Shiou SR, Yu Y, Chen S, Ciancio MJ, Petrof EO, Sun J, Claud EC.  Erythropoietin protects intestinal epithelial barrier function and lowers the incidence of experimental neonatal necrotizing enterocolitis.  J Biol Chem. 2011. PMID: 21262973; PMCID: PMC3069416 

Tao Y, Hart J, Lichtenstein L, Joseph L, Ciancio M, Hu S, Chang EB, Bissonnette M.    Inducible heat shock protein 70 prevents multifocal flat dysplastic lesions and invasive tumors in an inflammatory model of colon cancer.  Carcinogenesis.  30: 175-182, 2009. PMID: 19005184; PMCID: PMC2722142

Petrof EO, Musch MW, Ciancio MJ, Sun J, Hobert ME, Claud EC, Gewirtz AT, Chang EB. Flagellin is required for Salmonella-induced expression of heat shock protein Hsp25 in intestinal epithelium. Am J Physiol Gastrointest Liver Physiol. 294: 808-818, 2008. PMID: 18202113

*Hu S, *Ciancio MJ, Lahav M, Fujiya M, Lichtenstein L, Anant S, Musch MW, Chang EB. Translational inhibition of colonic epithelial heat shock proteins by interferon -gamma and TNF-alpha in IBD. * shared authorship   Gastroenterology.   133(6):1893-904, 2007. PMID: 18054561; PMCID:PMC2180161