Assistant Professor
Department of Physiology and Cell Biology
Department of Orthopedic Surgery and Rehabilitation
University of Arkansas for Medical Sciences
4301 W. Markham St. #505
Little Rock, AR 72205
E-Mail: snovak@uams.edu
Phone: 501-686-6482
Research Interests
Dr. Novak’s lab focuses on understanding the regeneration of the musculoskeletal system, with two main research areas: fracture healing and osteoarthritis. The overarching goals are to:
Investigate the mechanisms by which immune cells regulate fracture healing
Research has shown that the absence of T and B cells impairs bone healing. However, excessive pro-inflammatory signals can disrupt bone regeneration or cause fractures to fail to heal (non-union). Immune cells play key roles at various stages of the healing process:
- Injury and Inflammation: The initial injury triggers hematoma formation and infiltration of hematopoietic cells, followed by tissue clearance. A strong pro-inflammatory response begins the healing process, which is later balanced by anti-inflammatory signals.
- Stem Cell Expansion: Anti-inflammatory signals are essential for expanding skeletal stem and progenitor cells (SSPCs), which then differentiate into cartilage- and bone-forming cells.
- Resorption: In the final phase, osteoclasts, cells derived from a hematopoietic lineage, resorb the bony callus.
Although immune responses are most prominent during the early stages of bone healing, immune cells continue to play crucial roles throughout the regeneration process. Local cytokines and growth factors provide essential signals that promote angiogenesis, mesenchymal cell migration, proliferation, and differentiation, driving regeneration. However, the precise mechanisms regulating these stages remain unclear.
Explore how cytokines and angiogenic factors contribute to osteoarthritis development
Osteoarthritis (OA) is a degenerative joint disease with high prevalence in elderly and obese populations. Factors such as joint overuse, injury, and certain genetic polymorphisms contribute to OA progression. In healthy joints, articular cartilage provides smooth, frictionless lubrication for movement; however, in OA, this cartilage degenerates, leading to pain and impaired joint function. Articular cartilage has limited regenerative ability, and once injured, it does not regenerate effectively.
Understanding the mechanisms that control musculoskeletal regeneration is crucial for developing targeted therapies to enhance bone and cartilage healing and restore skeletal function.
Our lab utilizes a range of advanced techniques, including transgenic animals, lineage tracing, bone and cartilage injury models (e.g., fractures, femoral critical size defects, tibial and calvarial defects, parabiosis, destabilization of the medial meniscus, loading-induced joint injury), biomechanical testing, immunofluorescent microscopy, microCT, and scRNA-seq. These approaches help us uncover the underlying mechanisms governing bone and cartilage healing.
Representative Publications
- 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:e181073. PMCID: PMC11383173.
- 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. doi: 10.1038/s41536-023-00276-5. PMID: 36631491
- Novak S, Roeder E, Sinder BP, Adams DJ, Siebel CW, Grcevic D, Hankenson KD, Matthews BG, Kalajzic I. Modulation of Notch1 signaling regulates bone fracture healing. J Orthop Res. 2020 Nov;38(11):2350-2361. doi: 10.1002/jor.24650. Epub 2020 Mar 16. PMID: 32141629
- Novak S, Roeder E, Kalinowski J, Jastrzebski S, Aguila HL, Lee SK, Kalajzic I, Lorenzo JA, Osteoclasts Derive Predominantly from Bone Marrow-Resident CX3CR1+ Precursor Cells in Homeostasis, whereas Circulating CX3CR1+ Cells Contribute to Osteoclast Development during Fracture Repair. J Immunol. 2020 Feb 15;204(4):868-878. PMID: 31915261