Photo of Ivo Kalajzic, MD, PhD

Ivo Kalajzic, MD, PhD

Professor, Department of Regenerative Medicine and Skeletal Development

Professor, Genetics and Genome Sciences
Academic Office Location:
Center for Regenerative Medicine and Skeletal Development
UConn Health
263 Farmington Avenue
Farmington, CT 06030-3705
Phone: 860-679-6051
Fax: 860-679-2910
Website(s):

Skeletal Biology and Regeneration Graduate Program
Curriculum Vitae:
Education
DegreeInstitutionMajor
MDZagreb University School of MedicineMedicine
PhDSplit University School of MedicineBasic Medical Sciences - Genetics

Awards
Name of Award/HonorAwarding Organization
Outstanding research accomplishment award, team academiaMilitary Health Research Symposium (MHSRS)
Faculty mentoring AwardSchool of Dental Medicine, UConn Health.
Supplement to advance research (STAR award) NIAMS/NIHASBMR
Outstanding Researcher AwardSchool of Dental Medicine, UConn
Career Enhancement AwardAmerican Society of Bone and Mineral Research
Harold Frost Young Investigator AwardAmerican Society of Bone and Mineral Research
Young Investigator Award, Annual MeetingAmerican Society of Bone and Mineral Research
Fellowship AwardChildren Brittle Bone Foundation
John Haddad Young Investigator AwardAmerican Society of Bone and Mineral Research
Outstanding Presentation Award, Washington, DCEast Coast Connective Tissue Society Meeting
Michael Geisman Fellowship Award Osteogenesis Imperfecta Foundation
Name & DescriptionCategoryRoleTypeScopeStart YearEnd Year
Health Research Council of New Zealand Professional/Scientific OrganizationReviewerExternalInternational20242024
Veterans Health Administration RRDS Professional/Scientific OrganizationReviewerExternalNational20242024
FASEB conference advisory committeeAdvisory CommitteeReviewerExternalNational20212024
Research Excellence programResearch CommitteeReviewerUConn-StorrsState20212024
Osteogenesis imperfecta foundation Professional/Scientific OrganizationReviewerExternalNational20202020
SBSR-NIH study section Professional/Scientific OrganizationReviewerExternalNational20202025
ASBMR STAR award grants Professional/Scientific OrganizationReviewerExternalNational20202020
Mitacs accelerate proposal reviewProfessional/Scientific OrganizationReviewerExternalInternational20192019
TelethonProfessional/Scientific OrganizationReviewerExternalInternational20192019
Swiss National Science Foundation Professional/Scientific OrganizationReviewerExternalInternational20192021
Fonds National SuisseProfessional/Scientific OrganizationReviewerExternalInternational20192021
Loan Repayment Pediatric study section Professional/Scientific OrganizationReviewerExternalNational20182018
Czech Science Foundation Professional/Scientific OrganizationReviewerExternalInternational20182018
NIH BMBI study sectionProfessional/Scientific OrganizationReviewerExternalNational20172017
NIH Fellowship Review MeetingProfessional/Scientific OrganizationReviewerExternalNational20132015
Orthopedic Research SocietyProfessional/Scientific OrganizationMemberExternalNational2012
Endocrinology-B ENDB, VAProfessional/Scientific OrganizationReviewerExternalNational20122016
Peer Review Medical ProgramResearch CommitteeReviewerExternalNational20102010
ZRG1 MOSS-C04 special emphasis panel, NIHProfessional/Scientific OrganizationReviewerExternalNational20102010
American Society of Bone and Mineral ResearchProfessional/Scientific OrganizationMemberExternalNational2006
International Chinese Hard Tissue SocietyProfessional/Scientific OrganizationMemberExternalInternational2006

Isolation and characterization of different stages of cells within skeletal lineage.


My initial studies in the late 90’s have defined stages of osteoprogenitor differentiation into preosteoblast and osteoblast using visual marker- green fluorescent proteins. Based on this work we gained experience in using in vivo and in vitro animal models and various approaches including lineage tracing that will be important for the proposed studies. 


Using alpha-smooth muscle actin (aSMA) GFP to identify mesenchymal progenitor cells (MPCs), and CreERT2/reporter system as an in vivo lineage tracing approach we defined MPCs in vivo as a perivascular population of cells within the bone marrow and fibroblastic MPC within periosteum. The main progress of this work was in defining population of mesenchymal stem/progenitor cells and characterizing gene expression of isolated cell populations.


1. Kalajzic I., Kalajzic Z, Kaliterna M, Gronowicz G, Clark SH, Lichtler AC and Rowe DW. Use of Col1a1GFP transgenes to identify subpopulations of cells at different stages of the osteoblast lineage. J Bone Miner Res.  2002,17:15-25.PMID: 11771662.


2.Matthews BG, Novak S, Sbrana FV, Funnell JL, Cao Y, Buckels EJ, Grcevic D, Kalajzic I. Heterogeneity of murine periosteum progenitors involved in fracture healing. Elife. 2021 Feb 9;10:e58534 PMID: 33560227.


3. Matic I, Matthews BG, Wang X, Dyment NA, Worthley DL, Rowe DW, Grcevic D, Kalajzic I. Quiescent Bone Lining Cells Are a Major Source of Osteoblasts During Adulthood. Stem Cells. 2016 Dec;34(12):2930-2942. PMID: 27507737


Mechanisms regulating commitment of mesenchymal progenitor cells (MPCs).


Using state of the art techniques of bulk seq, singe cell RNA sequencing position us to be successful in completing proposed studies. We extended cell lineage tracing work to understanding the mechanisms that regulate commitment and osteogenic differentiation of these cells using models of bone repair. We have identified changes in Notch signaling as a critical regulator of the commitment of MPCs towards chondrogenic and osteogenic lineages.


4.Novak S, Tanigawa H, Singh V, Root SH, Schmidt TA, Hankenson KD, Kalajzic I. Endothelial to mesenchymal Notch signaling regulates skeletal repair. JCI Insight. 2024 May 23;9(12):e181073. PMID: 38781018


5. Novak S, Madunic J, Shum L, Vucetic M, Wang X, Tanigawa H, Ghosh M, Sanjay A, Kalajzic I. PDGF inhibits BMP2-induced bone healing. NPJ Regen Med. 2023 Jan 11;8(1):3. PMID: 36631491


6. Matthews BG, Grcevic D, Wang L, Hagiwara Y, Roguljic H, Joshi P, Shin D-G, Adams DJ, and Kalajzic I. Analysis of αSMA-labeled progenitor cell commitment identifies Notch signaling as an important pathway in fracture healing. J Bone Miner Res. 2014;29(5):1283-944 PMID: 24190076.


Understanding pathophysiology of Osteogenesis imperfecta (OI).


Experience in bone biology and evaluating bone formation and resorption is important part of the proposed work. Additionally proposed translational approaches require knowledge on evaluation of bone physiology and pathophysiology. Evaluating treatment of OI using pharmacological compounds evaluation of success of cellular therapy will benefit our proposed work.   


We have utilized the OI model (OIM) to study the pathophysiology of OI, defining a high turnover state and identifying potential mechanisms of this increase in bone remodeling. Based on our previous work indicating the importance of inflammatory cytokines in osteoclast induction in the OIM mice, we evaluated treatment of the OIM mice with anti-TNFa compound. In addition, we also, evaluated bone directed transplantation as to treat OI, that provides a novel translational approach.


7.         Matthews BG, Roeder E, Wang X, Aguila HL, Lee SK, Grcevic D, Kalajzic I. Splenomegaly, myeloid lineage expansion and increased osteoclastogenesis in osteogenesis imperfecta murine. Bone. 2017 Oct;103:1-11. PMID: 28600151.


8.         Sinder BP, Novak S, Wee NKY, Basile M, Maye P, Matthews BG, Kalajzic I. Engraftment of Skeletal Progenitor Cells by Bone Directed Transplantation Improves Osteogenesis Imperfecta Murine Bone Phenotype. Stem Cells. 2020 Apr;38(4):530-541. PMID: 31859429.


Defining “neuronal regulation” of bone formation.


Our current work is on understanding neuronal regulation of bone healing. We are currently funded to evaluate the role of CGRP-CLR on fracture as an effector of sensory signaling. We also, developed NPY overexpression mice and a conditional knockout mouse for Neuropeptide Y, a sympathetic signaling component. These models will serve as basis of the current proposal.


We developed studies into how osteocytes use neuronal-type molecules in regulation of bone formation. We have identified neuropeptide Y (NPY) as an osteocyte factor that can modulate osteogenic lineage activity. The proposed studies are focused of deciphering the role of NPY as a local (bone microenvironment) regulator of bone mass during normal bone homeostasis and fracture healing and evaluating theraputi9c approach using modulation of this signaling pathway.


9.         Wee NKY, Sinder BP, Novak S, Wang X, Stoddard C, Matthews BG, Kalajzic I. Skeletal phenotype of the neuropeptide Y knockout mouse. Neuropeptides. Neuropeptides. 2019 Feb;73:78-88. PMID: 30522780.


10.       Wee NKY, Vrhovac Madunic I, Ivanisevic T, Sinder PB, Kalajzic I. Divergent effects of peripheral and global neuropeptide Y deletion. J Musculoskelet Neuronal Interact. 2020 Dec 1;20(4):579-590. PMID: 33265087.

Accepting Lab Rotation Students: Spring 1 block 2026

Journal Articles

Conference Papers

Editorials

Reviews