Manoj Muthukuru, BDS, MMSc (Periodontology), PhD
Assistant Professor, Department of Periodontics
Adjunct Assistant Professor, Department of Oral Health Sciences
Immunoregulation during chronic oral mucosal inflammation
Appropriate immune response is required for effective elimination of infectious agents. Mucosal surfaces such as the gut and the oral mucosa are exposed to an enormous microbial burden, which would overwhelm immune homeostasis, if not for various mechanisms that regulate and dampen the inflammatory response. Blunting the inflammatory response potentially protects the host from exuberant host tissue damage. The loss of such regulatory mechanisms is associated with excessive systemic and mucosal inflammatory diseases. On the contrary, these regulatory mechanisms might represent the proverbial “double-edged sword”, by impairing the activities involved in effective elimination of the infectious agents.
Our research interest is to study the regulatory mechanisms in the immune / inflammatory responses associated with chronic oral mucosal inflammatory conditions such as chronic periodontitis. We employ cell biology and molecular biology tools to study the cell signaling, regulation of transcription factors and other relevant functional analysis. We study immune responses to bacterial structures such as Lipopolysaccharide by employing dendritic cells and langerhans cells generated from stem cells from the cord blood. We also employ novel approaches to study T cells ex vivo, from mucosal tissues.
Microenvironment conditioning for optimizing bone regeneration
A well regulated microenvironment during wound healing is desirable in promoting the overall growth and regeneration of the host tissues. Microbial colonization of the healing wound, which presents as a common problem may exaggerate the inflammatory response. Such complications are especially faced by clinicians while attempting to regenerate tissues, such as bone. These excessive inflammatory responses during wound healing trigger tissue destruction through the activation of tissue collagenases. The inhibitors of these tissue metabolic enzymes are known to promote tissue regeneration. Also, growth promoting factors directly augment cellular proliferation and tissue regeneration.
Our research focuses on studying and engineering novel strategies to condition the wound healing microenvironment, in order to enhance bone tissue regeneration. In vitro cell culture and in vivo animal models are employed to study the growth and differentiation of cells associated in bone regeneration and also studies focus on synthesis and remodeling of the bone matrix. Drug delivery systems by employing naturally present connective tissue matrix molecules are developed with the collaboration from Central Leather Research Institute (CLRI), India.
- Clark RA, Huang SJ, Murphy GF, Mollet IG, Hijnen D, Muthukuru M, Schanbacher CF, Edwards V, Miller DM, Kim JE, Lambert J, Kupper TS. Human squamous cell carcinomas evade the immune response by down-regulation of vascular E-selection and recruitment of regulatory T cells. J Exp Med. 2008 Sep 29;205(10):2221-34.
- Muthukuru M and Cutler CW. Antigen capture of Porphyromonas gingivalis by human macrophages is enhanced but killing and antigen presentation are reduced by endotoxin tolerance. Infection and Immunity. 2008 Feb;76(2):477-85.
- Muthukuru M and Cutler CW. Upregulation of Immunoregulatory Src Homology Molecule Containing Inositol Phosphatase and Mononuclear Cell Hyporesponsiveness in Oral Mucosa during Chronic Periodontitis. Infection and Immunity. 2006 Feb;1431-1435.
- Muthukuru M. Endotoxin Tolerance as a Novel Regulatory Mechanism of the Oral Mucosal Innate Immune Response during Chronic Periodontitis. Thesis; Manuscript submitted to the Graduate School, Stony Brook University towards partial fulfillment of the doctoral (Ph.D.) degree. June 2005.
- Muthukuru M, Jotwani R, Cutler CW. Oral Mucosal Tolerance Induction in Chronic Periodontitis. Infection and Immunity. Feb. 2005, 687-694.
- Jotwani R, Muthukuru M, Cutler CW. Increase in HIV receptors/co-receptors/alpha – defensins in inflamed human gingiva. J Dent Res. 2004, May;83(5):371-7