Professor Meenakshi Chellaiah, PhD

Meena Chellaiah

My lab research focuses on bone remodeling due to modulation in osteoclasts and osteoblasts in response to various treatments and cancer metastasis to bone. I have provided a summary of the ongoing projects in the lab. 

 

Research Interests

  • Project 1: My laboratory is the first to document L-plastin's role (LPL) in osteoclast sealing ring formation and bone resorption in the osteoclast project. L-plastin (LPL) was identified as a potential regulator of the actin-bundling process involved in forming nascent sealing zones (NSZs), which are precursor zones for mature sealing rings. Genetic deletion of LPL in mice demonstrated decreased eroded perimeters and increased trabecular bone density. TAT-fused cell-penetrating small molecular weight LPL peptide (TAT- MARGSVSDEE, denoted as an inhibitory LPL peptide) attenuated the formation of NSZs and sealing rings and impaired bone resorption in vitro in osteoclasts (Figure below). 
  • Subsequently, we injected aging C57BL/6 female mice (36 weeks old) subcutaneously with the inhibitory and scrambled peptides of LPL for 14 weeks. Micro-CT and histomorphometry analyses demonstrated an increase in trabecular bone density of femoral and tibial bones with no change in cortical thickness in mice injected with the inhibitory LPL peptide. The LPL peptide approach in bone loss is novel. We will examine the impacts of the LPL inhibitory peptide on other models that display bone loss due to osteoclast activation. To improve stability and sustain release, we are using nanotechnology, which was shown to have more advantages in delivering proteins and peptides. 
  • This inhibitory LPL peptide has been patented, and it has been publicly available at http://www.uspto.gov/patft/. The patent application number and date are provided by the United States Patent and Trademark Office (United States Department of Commerce). 
  • Project 2: Recently, we developed another project to determine C-phycocyanin (C-PC) effect on LPS regulated osteoclastogenesis. C-PC strongly inhibited the early stage of osteoclast differentiation, thus significantly suppressing RANKL- TNF-alpha- and LPS- mediated osteoclastogenesis. Results from our studies highlighted a possible osteoclastogenesis process during bacterial-mediated osteolytic infections. Therefore, targeting LPS-induced osteoclastogenesis could be a promising therapeutic strategy to inhibit inflammatory bone loss in diseases such as periodontitis, rheumatoid arthritis, etc. Future investigations will use proper animal model systems to determine C-PC's effect on bone loss in vivo. 
  • Project 3: We are using dental stem cells to generate osteoblast-like cells.  Our focus here is how these stem cells can be utilized with osteoinductive materials and stimulatory factors (e.g., Methylsulfonylmethane (MSM)) to induce bone formation.  We found that MSM can increase the osteogenesis process and regulate the matrix's mineralization via transglutaminase enzyme in SHED cells (stem cells).  We continue to investigate the effect of MSM in an aging mice model system to validate its impact on bone formation in vivo. 
  • Project 4: Prostate cancer (PCa) is the second leading cause of cancer-related death in men in the United States, partially due to metastatic spread to secondary sites in the bone, brain, lymph nodes, and visceral organs. Here, we examine the mechanisms that can facilitate PCa progression/metastasis. We identified the critical role of the intracellular domain of CD44 in metastasis relevant events, including migration and tumorigenesis. For the first time in PCa, we showed the consequence of CD44 intracellular domain cleavage on tumorigenesis and the sequence-specific interaction with RUNX2, a transcriptional factor involved in the transcription of metastasis-related genes. Our results allude to CD44-ICD as a novel therapeutic target in cancer cells that express CD44.  Future studies will focus on CD44-ICD signaling, interactions, and tumorigenesis.

Publications pertinent to the projects mentioned above are provided below. 

Osteoclasts were stained for actin with rhodamine-phalloidin, and confocal images of osteoclasts are shown (ad). Osteoclasts plated on dentine matrix incubated with scrambled (a and c) LPL peptide in the presence of TNF-α for 2-3h demonstrate nascent sealing zones (NSZs, a; indicated by arrows) and for 8-10h demonstrate mature sealing rings (SRs, c; indicated by asterisks). Cells incubated with inhibitory peptide (b and d) fail to demonstrate either NSZs (b) or SRs (d).  An arrowhead points to a small sealing ring in (d). Scale Bar-25 µm. e and f Dentine resorption assay in vitro: Osteoclasts plated on dentine matrix were incubated with scrambled (e) or inhibitory (f) LPL peptide in the presence of TNF-α for 10–14 h. Resorption pits were photographed under a 40X objective of phase-contrast microscopy (magnification is ×400). Resorbed areas of approximately ~25–30 pits were quantified from three slices per treatment/experiment (n = 3) and averaged over two different experiments. Statistical analysis of the pit area was performed by Student’s test and provided at the bottom. ***P < 0.001 vs. scrambled peptide transduced osteoclasts (mean ± SEM). [Bone Res 9, 22 (2021]

 

 Peer-Reviewed Publications Since 2017

  1. Aljohani H, Stains JP, Majumdar S, Srinivasan D, Senbanjo L, Chellaiah MA. Peptidomimetic inhibitor of L-plastin reduces osteoclastic bone resorption in aging female mice. Bone Res. 2021 Apr 9;9(1):22. doi: 10.1038/s41413-020-00135-9. PubMed PMID: 33837180.
  2. AlQranei MS, Senbanjo LT, Aljohani H, Hamza T, Chellaiah MA. Lipopolysaccharide- TLR-4 Axis regulates osteoclastogenesis independent of RANKL/RANK signaling. BMC Immunol. 2021 Mar 25;22(1):23. doi: 10.1186/s12865-021-00409-9. PubMed PMID: 33765924; PubMed Central PMCID: PMC7995782.
  3. Senbanjo LT, AlJohani H, AlQranei M, Majumdar S, Ma T, Chellaiah MAIdentification of sequence-specific interactions of the CD44-intracellular domain with RUNX2 in the transcription of matrix metalloprotease-9 in human prostate cancer cells. Cancer Drug Resist. 2020 3rd Quarter;3(3):586-602. doi: 10.20517/cdr.2020.21. Epub 2020 Aug 21. PubMed PMID: 33062960; PubMed Central PMCID: PMC7556329.
  4. Chellaiah MA. Regulation of Bone Resorption by Osteoclasts-an Overview. Medical Research Archives. 2020 August; 8(9):1-10.
  5. Chellaiah MAOsteoclast Cytoskeleton, Podosome, Motility, Attachment, and Signaling by Receptors. Encyclopedia of Bone Biology: Zaidi, M (ed.) Oxford: Academic Press. 2020 July; 1:236-250.
  6. AlQranei MS, Chellaiah MAOsteoclastogenesis in periodontal diseases: Possible mediators and mechanisms. J Oral Biosci. 2020 Jun;62(2):123-130. doi: 10.1016/j.job.2020.02.002. Epub 2020 Feb 17. Review. PubMed PMID: 32081710; PubMed Central PMCID: PMC7329621.
  7. AlQranei MS, Aljohani H, Majumdar S, Senbanjo LT, Chellaiah MAC-phycocyanin attenuates RANKL-induced osteoclastogenesis and bone resorption in vitro through inhibiting ROS levels, NFATc1 and NF-κB activation. Sci Rep. 2020 Feb 13;10(1):2513. doi: 10.1038/s41598-020-59363-y. PubMed PMID: 32054921; PubMed Central PMCID: PMC7018981.
  8. Chellaiah MA, Moorer MC, Majumdar S, Aljohani H, Morley SC, Yingling V, Stains JP. L-Plastin deficiency produces increased trabecular bone due to attenuation of sealing ring formation and osteoclast dysfunction. Bone Res. 2020;8:3. doi: 10.1038/s41413-019-0079-2. eCollection 2020. PubMed PMID: 31993243; PubMed Central PMCID: PMC6976634.
  9. Aljohani H, Senbanjo LT, Chellaiah MAMethylsulfonylmethane increases osteogenesis and regulates the mineralization of the matrix by transglutaminase 2 in SHED cells. PLoS One. 2019;14(12): e0225598. doi: 10.1371/journal.pone.0225598. eCollection 2019. PubMed PMID: 31805069; PubMed Central PMCID: PMC6894810.
  10. Senbanjo LT, Chellaiah MACD44 cleavage product CD44-intracellular domain regulates gene transcription and tumorigenesis. Cancer Studies and Therapeutics. 2019 September; 4(4):1-2.
  11. Senbanjo LT, AlJohani H, Majumdar S, Chellaiah MACharacterization of CD44 intracellular domain interaction with RUNX2 in PC3 human prostate cancer cells. Cell Commun Signal. 2019 Jul 22;17(1):80. doi: 10.1186/s12964-019-0395-6. PubMed PMID: 31331331; PubMed Central PMCID: PMC6647163.
  12. Majumdar S, Wadajkar AS, Aljohani H, Reynolds MA, Kim AJ, Chellaiah MAEngineering of L-plastin Peptide-Loaded Biodegradable Nanoparticles for Sustained Delivery and Suppression of Osteoclast Function In Vitro. Int J Cell Biol. 2019;2019:6943986. doi: 10.1155/2019/6943986. eCollection 2019. PubMed PMID: 31191656; PubMed Central PMCID: PMC6525930.
  13. Homayounfar N, Khan MM, Ji Y, Khoury ZH, Oates TW, Goodlett DR, Chellaiah M, Masri R. The effect of embryonic origin on the osteoinductive potential of bone allografts. J Prosthet Dent. 2019 Apr;121(4):651-658. doi: 10.1016/j.prosdent.2018.09.003. Epub 2018 Dec 28. PubMed PMID: 30598313.
  14. Chellaiah MA, Ma T, Majumdar S. L-plastin phosphorylation regulates the early phase of sealing ring formation by an actin-bundling process in mouse osteoclasts. Exp Cell Res. 2018 Nov 1;372(1):73-82. doi: 10.1016/j.yexcr.2018.09.014. Epub 2018 Sep 21. PubMed PMID: 30244178; PubMed Central PMCID: PMC6181588.
  15. Chellaiah MA, Majumdar S, Aljohani H. Peptidomimetic inhibitors of L-plastin reduce the resorptive activity of osteoclast but not the bone-forming activity of osteoblasts in vitro. PLoS One. 2018;13(9):e0204209. doi: 10.1371/journal.pone.0204209. eCollection 2018. PubMed PMID: 30248139; PubMed Central PMCID: PMC6152981.
  16. Srinivasan D, Senbanjo L, Majumdar S, Franklin RB, Chellaiah MAAndrogen receptor expression reduces stemness characteristics of prostate cancer cells (PC3) by repression of CD44 and SOX2. J Cell Biochem. 2018 Sep 11; 120(2):2413-2428. doi: 10.1002/jcb.27573. [Epub ahead of print] PubMed PMID: 30206982; PubMed Central PMCID: PMC6411465.
  17. Senbanjo LT, Chellaiah MACD44: A Multifunctional Cell Surface Adhesion Receptor Is a Regulator of Progression and Metastasis of Cancer Cells. Front Cell Dev Biol. 2017;5:18. doi: 10.3389/fcell.2017.00018. eCollection 2017. Review. PubMed PMID: 28326306; PubMed Central PMCID: PMC5339222.

Lab Personnel (Present and Past)

Current Graduate Students 
  • Marjan Sharifi DDS (since 2019)
  • Mahsa Sharifi DDS (since 2020)
Past members since 2000
  • Post-doctoral fellows (2000 to 2020) 
    • Rajat Biswas PhD
    • Venkatasababa Samanna PhD
    • Tao Ma PhD
    • Aditi Gupta PhD
    • Sunipa Majumdar PhD
    • Linda Senbanjo PhD  
  • Research Fellow (2016-2018)
    • Deepa Srinivasan MS  
  • Graduate students (2004-2020)
    (graduated years in parenthesis)
    • Bhavik Desai (2008)
    • Brian Robertson (2010)
    • Linda Senbanjo (2019)
    • Hanan Aljohani (2020)
    • Mohammed AlQranei (2020)
  • Research Assistants 
    • David Yuen (2000-2002)
    • Kavitha Sadashivaiah (2009)
  • Exchange Visitors
    • Ganglao Gao, a physician from China (2013)
    • Lei Lei (China; 2012)
    • Han Ji Young (Korea; 2012)
    • Hongzhi Zhou (Physician and Professor from China Came on Sabbatical; 2011)
    • Wei Cao (Ph.D. candidate from Dr. Wantao Chen laboratory; China; 2010)

Dr. Chellaiah also supports lab rotations of Ph.D. students as well as residents' and Master students' projects at the School of Dentistry and School of Medicine, University of Maryland, Baltimore.

Education and Training

1985 Ph.D., Biochemistry Madurai Kamaraj University, India
1975-1977 M.Sc., Zoology Madurai Kamaraj University, India
1972-1975 B.Sc., Zoology Madurai Kamaraj University, India 

 

1997-1999 Research Instructor, Department of Medicine; Washington University School of Medicine, St. Louis
1992-1997 Research Associate, Department of Medicine; Jewish Hospital, St. Louis, Missouri
1990-1992 Research Associate, Department of Pathology; Jewish Hospital of St. Louis, St. Louis, Missouri
1987-1990 Postdoctoral Fellow, Department of Biochemistry & Molecular Biology; St. Louis University, St. Louis, Missouri
1986-1987 Research Associate, Department of Microbiology; Madurai Kamaraj University, Madurai, India
1977-1979 Research Assistant, Department of Biochemistry; Madurai Kamaraj University, Madurai, India

Employment History 

August 2014‑Present Professor, Department of ODS; SOD, University of Maryland, Baltimore
2007 Aug-July 2014 Associate Professor, Department of ODS; SOD, University of Maryland, Baltimore
2001-present Adjunct Assistant Professor, Molecular and Cell Biology Graduate program; University of Maryland, Baltimore
July 2000-2007 Assistant Professor, Department of BMS; SOD, University of Maryland, Baltimore
1999-June 2000 Research Assistant Professor, Department of Medicine; Washington University School of Medicine, St. Louis, Missouri

Honors and Awards 

2010-2013 NIH-NIAMS Bridge Award ($337 500)
2009-2010 American Society for Bone and Mineral Research Award ($50,000)
2001-2002 DRIF: University of Maryland, Dental School $4500
2002-2003 DRIF: University of Maryland, Dental School $4500
1999-2000 Barnes-Jewish Research Foundation, St. Louis, MO $50,000
1996-1997 Barnes-Jewish Research Foundation, St. Louis, MO $50,000
1991-1992 NIADDK training grant award
1989-1990 NRS training grant award
1980-1985 Council of Scientific and Industrial Research Award for Ph.D. program
1979 University IV Rank Holder in MSc (India)
1977-1979 Awarded National Merit Scholarship for Master program (MSc) in India
1977 University II Rank Holder in bachelor's degree (BSc) for which National Merit Scholarship was awarded (India)

Grants

Active Grant

  • Proposal Title: "L-Plastin: A Novel Target for Intervention in the Treatment of Osteoporosis." Principle Investigator. NIH/NIAMS. NIH R01 AR066044-01 (09/15/2014-08/30/2019). No-cost extension until 2021

Completed Grants

  • Competitively renewed twice R01 Grants (08-01-1999 to 06- 30-2013): Proposal Title: "Regulation of signaling in osteoclast bone resorption" NIH/NIAMS. Principle Investigator. 2 R01 AR-46292-9A1 was competitively renewed twice during this period.
  • Bridge Award for one year: Principle Investigator. Agency: American Society for Bone and Mineral Research
  • F30 Student Grant (Awarded for two years): Role-Mentor. Awarded to student Brian Robertson (graduate student in DDS/Ph.D. program). Title: The role of osteopontin in cancer progression and metastasis Period: 06-01-07 to 06-31-09. NIH-NIDCR. Type: 1 F30 DE018308-01