Rajaram Gopalakrishnan, BDS, PhD

Dr. Raj Gopalakrishnan is Professor and director of the Division of Oral and Maxillofacial Pathology, Department of Developmental and Surgical Sciences, School of Dentistry, University of Minnesota. He is also a member of the Oral Biology Graduate program at the School of Dentistry.

Dr. Gopalakrishnan received his Bachelor of Dental Surgery (BDS) degree from University of Madras, Chennai, India in 1991 and completed a residency in Oral and Maxillofacial Pathology from The Ohio State University College of Dentistry in 1995. He subsequently obtained a PhD in Pathology from The Ohio State University in 1999, and joined the laboratory of Dr. Renny Franceschi at the University of Michigan as a post doctoral fellow.

In 2002, he became an assistant professor at the University of Minnesota.

Dr. Gopalakrishnan’s overall research focuses on the mechanisms regulating bone remodeling. Major experimental approaches include use of global and bone-specific knockout and overexpressing transgenic mice, histological analyses of bone, static and dynamic histomorphometry, and signaling and transcriptional studies using basic molecular and cell biological techniques.

Role of BMP and Twsg-1 in osteoclastogenesis
Dr. Gopalakrishnan's research demonstrates that mice deficient in twisted gastrulation (Twsg1), an extracellular binding protein of BMP, show osteopenia due to enhanced osteoclastogenesis mediated through increased BMP signaling. Follow up publications have shown that BMP2 can directly activate osteoclasts and Twsg1 can inhibit osteoclast differentiation. Current studies focus on the function of non-canonical and canonical BMP pathways during osteoclastogenesis and regulation of these pathways in various stages of osteoclast formation. The long-term goal of Dr. Gopalakrishnan's research is to understand the regulation of osteoclast formation to enable better diagnostic and therapeutic interventions into the bone remodeling process.

PrKD signaling and osteoclasts differentiation
In collaboration with Dr. Eric Jensen and Dr. Kim Mansky, Dr. Gopalakrishnan's lab studies the effect of the protein kinase D (PrKD) pathway in osteoclastogenesis, showing PrKD activity is critical for osteoclast fusion through increased expression of DC-STAMP, a key osteoclast fusion gene. Recent publications showed that PrKD2 is the main PrKD isoform expressed in osteoclastic cells, and RNAi against PrKD2 or treatment with the PrKD inhibitor CID755673 reduced expression of DC-STAMP leading to decreased osteoclast fusion. Current studies are focused on understanding the mechanisms by which PKD2 regulates osteoclast fusion.

Functional significance of HDAC7 in osteoclast formation
Dr. Gopalakrishnan’s lab, in a co-investigation with Dr. Jensen and Dr. Mansky, recently identified histone deacytelase 7 (HDAC7) as a novel regulator of osteoclast formation. In vitro data showed that suppression of HDAC7 enhanced differentiation of osteoclasts from bone marrow macrophage cultures, while overexpression of HDAC7 inhibited osteoclast formation. Osteoclasts from HDAC7 null mice are larger in size, display increased resorption activity, and show increased expression of MITF/PU.1 target genes including DC-STAMP, OSCAR, cathepsin K and v-ATPase V0 subunit d2. Current studies focus on the interaction between HDAC7 and MITF/PU.1 transcription factors and the mechanism(s) for HDAC7 regulation of osteoclast formation.

Epidemiology, risk factors and pathogenesis of BRONJ
Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a significant and serious oral complication of long-term intravenous bisphosphonate (BP). Through a case-control study, Dr. Gopalakrishnan’s research showed that BRONJ cases had significantly more missing teeth, higher average clinical attachment loss (CAL), and higher percentage of sites with CAL ? 3mm than controls. In a related project using salivary proteomics, Dr. Gopalakrishnan and his collaborators identified 200 proteins differentially expressed in BRONJ patients. A majority of these proteins are predicted to have a role in drug metabolism, immunological and dermatological disease. Current and future studies are focused on clarifying the roles of these proteins in BRONJ.
 

Organogenesis, Fellowship
University of Michigan

Oral and Maxillofacial Pathology, Residency
The Ohio State University

Bone Biology, Visiting Scholar
University of Michigan

Award: Minnesota Craniofacial Research Training Program
Principal Investigator: Mansky, Kim
Sponsoring Organization: NIH NIDCR NATL INST OF DENTAL
Award Dates: 2017 - 2022

Award: Novel targeted treatment strategy for invasive and resis
Principal Investigator: Khammanivong, Ali
Sponsoring Organization: PARDEE FDN
Award Dates: 2016 - 2018

Award: Role of HDAC7 in Osteoclast Differentiation
Principal Investigator: Mansky, Kim
Sponsoring Organization: NIH NIAMS NATL INST OF ARTHRIT
Award Dates: 2013 - 2016

Award: Minnesota Craniofacial Research Training Program
Principal Investigator: Herzberg, Mark C
Sponsoring Organization: NIH NIDCR NATL INST OF DENTAL
Award Dates: 2012 - 2016

Award: Gravitational Regulation of Osteoblast Genomics and Meta
Principal Investigator: Hammer, Bruce E
Sponsoring Organization: NIH NATL INST OF BIOMEDICAL IM
Award Dates: 2011 - 2017

Award: Gravitational Regulation of Osteoblast Genomics and Meta
Principal Investigator: Hammer, Bruce E
Sponsoring Organization: NIH NATL INST OF BIOMEDICAL IM
Award Dates: 2011 - 2017

Award: Periodontal Disease as a Risk Factor for ONJ
Principal Investigator: Gopalakrishnan, Rajaram
Sponsoring Organization: NIH NIDCR NATL INST OF DENTAL
Award Dates: 2010 - 2013

Award: Periodontal Disease as a Risk Factor for ONJ
Principal Investigator: Gopalakrishnan, Rajaram
Sponsoring Organization: NIH NIDCR NATL INST OF DENTAL
Award Dates: 2010 - 2013

Award: Periodontal Disease as a Risk Factor for ONJ
Principal Investigator: Gopalakrishnan, Rajaram
Sponsoring Organization: NIH NIDCR NATL INST OF DENTAL
Award Dates: 2010 - 2013

Award: Function of HDAC7 in Osteoblasts
Principal Investigator: Jensen, Eric David
Sponsoring Organization: NIH NIDCR NATL INST OF DENTAL
Award Dates: 2010 - 2012

Award: Role of Twisted Gastrulation in Osteoclastogenesis
Principal Investigator: Gopalakrishnan, Rajaram
Sponsoring Organization: NIH NIAMS NATL INST OF ARTHRIT
Award Dates: 2010 - 2016

Award: Role of Twisted Gastrulation in Osteoclastogenesis
Principal Investigator: Gopalakrishnan, Rajaram
Sponsoring Organization: NIH NIAMS NATL INST OF ARTHRIT
Award Dates: 2010 - 2016

Award: Role of Twisted Gastrulation in Osteoclastogenesis
Principal Investigator: Gopalakrishnan, Rajaram
Sponsoring Organization: NIH NIAMS NATL INST OF ARTHRIT
Award Dates: 2010 - 2016

Award: The effect of Bisphosphonates on wound healing after too
Sponsoring Organization: ORAL & MAXILLOFACIAL SURGERY FOUNDATION
Award Dates: 2008 - 2010

Award: Regulation of Runx2 Transcriptional Activity
Principal Investigator: Gopalakrishnan, Rajaram
Sponsoring Organization: MAYO CLINIC ROCHESTER
Award Dates: 2008 - 2009

Award: Regulation of Runx2 Transcriptional Activity
Principal Investigator: Gopalakrishnan, Rajaram
Sponsoring Organization: MAYO CLINIC ROCHESTER
Award Dates: 2008 - 2008

Award: Twisted Gastrulation and Mandibular Arch Morphogenesis
Principal Investigator: Petryk, Anna
Sponsoring Organization: NIH NIDCR NATL INST OF DENTAL
Award Dates: 2007 - 2013