Maria A. Serrat, Ph.D.

Assistant Professor

Department: Anatomy and Pathology

Research Cluster: Neuroscience and Development Biology

Offices: BBSC 301L, MEB 207 | Labratory: MEB 206

Email: serrat@marshall.edu

Research Interest

Ambient temperature and physical activity have a surprising impact on bone length, but it is unclear how such common variables regulate growth of the postnatal skeleton. We study environmental inputs on bone elongation in growth plates, the regions of cartilage where bone lengthening occurs. Our long-term goal is to identify the physiological mechanisms underlying temperature- and exercise- enhanced bone elongation in the growth plate, with the intent of finding new ways to potentially treat growth impediments in children. We employ whole animal and bone culture models to test specific hypotheses about environmental effects on the growth plate matrix, its vasculature, and nutrient supply. We use a variety of tools such as live animal imaging; histology and immunostaining; fluorochrome bone labeling; micro-CT analysis; and fluorescent microsphere blood flow assays. Our research is important for an evolutionary understanding of limb length variation among mammals in different environments and may aid in developing more effective treatments for childhood growth disorders.

Laboratory Projects

Laboratory Projects

Imaging skeletal growth plates using in vivo multiphoton microscopy

Figure 3. In vivo multiphoton image of blood vessels in the plexus surrounding the tibial growth plate of a live, anesthetized 5-week-old mouse. Orientation matches Figure 1. Vessels were visualized using a multiphoton microscope after an intravenous injection of fluorescein. Plasma is red and blood cells appear as dark shadows within the vessels. The collagen-rich perichondrium around the growth plate (green-gray pseudocolor) was visualized by second harmonic generation (SHG), a robust signal from unstained collagen that is unique to multiphoton excitation. SHG allows collagenous structures to be identified without injecting stains or dyes. Imaging was done by Maria Serrat on a Leica TCS SP5 II Multiphoton Microscope housed in the Molecular and Biological Imaging Center at Marshall University (image modified from Serrat, 2014, Comprehensive Physiology, 4:621-55, Copyright 2014 American Physiological Society).

Multiphoton microscopy is an emerging technology for live animal imaging that offers exciting possibilities for the study of growth plate dynamics in vivo. In collaboration with colleagues at Cornell University, we developed a unique platform for imaging intact skeletal growth plates that we use to assess how systemic regulators arrive at and move within the cartilage matrix of the growth plate under various experimental conditions. This system provides a new mechanism for understanding the physiological regulation of bone growth through the ability to dynamically measure changes in molecular transport to the growth plate of a living animal (Fig. 3). Using biologically-inert dextrans as size-proxies for systemic regulators, we have shown that heat can increase real-time entry of large molecules into growth plate cartilage in vivo (Serrat, Efaw, and Williams, 2014). We are now using fluorescently-labeled proteins to quantify heat-enhanced access of biologically-active molecules into growth plates of live, intact mice.

Unilateral heating to lengthen extremities of growing mice

Fig. 4 Thermal Image of Mice during a Limb Heating Experiment (Serrat Lab) Limb heating experiments are being done in the Serrat Lab to study mechanisms underlying heat-enhanced bone elongation. Thermal image of juvenile mice on a heating pad (left) shows the temperature differential between heat-treated and non-treated sides. Limbs are equilibrated to 40C during the daily treatments. Digital image (right) shows foam separators that are used to keep the non-treated side at a cooler 30C. Images captured June 2014 by Ph.D. student Holly Tamski and Maria Serrat, Ph.D.

Selected Publications

Selected Publications

Environmental temperature impact on bone and cartilage growth.
Serrat MA. Compr Physiol. 2014 Apr;4(2):621-55. doi: 10.1002/cphy.c130023.
PMID: 24715562 [PubMed - in process]

Hindlimb heating increases vascular access of large molecules to murine tibial growth plates measured by in vivo multiphoton imaging.
Serrat MA, Efaw ML, Williams RM. J Appl Physiol (1985). 2014 Feb 15;116(4):425-38. doi: 10.1152/japplphysiol.01212.2013. Epub 2013 Dec 26. PMID: 24371019 [PubMed - in process]

Allen’s rule revisited: temperature influences bone elongation during a critical period of postnatal development.
Serrat MA. Anat Rec (Hoboken). 2013 Oct;296(10):1534-45. doi: 10.1002/ar.22763. Epub 2013 Aug 19. PMID: 23956063 [PubMed - indexed for MEDLINE]

Exercise mitigates the stunting effect of cold temperature on limb elongation in mice by increasing solute delivery to the growth plate.
Serrat MA, Williams RM, Farnum CE. J Appl Physiol (1985). 2010 Dec;109(6):1869-79. doi: 10.1152/japplphysiol.01022.2010. Epub 2010 Oct 7. PMID: 20930127 [PubMed - indexed for MEDLINE] Free PMC Article This paper used in vivo multiphoton microscopy to image growth plate cartilage with collaborators at Cornell University.

Serrat MA. Measuring bone blood supply in mice using fluorescent microspheres. Nature Protocols. 4(12): 1749-58. 2009. Single-author paper utilizing techniques developed by Dr. Serrat while she was a student at Kent State University.

Laboratory Personnel

Gabriela Ion, Ph.D. – Research Instructor, Department of Anatomy and Pathology
Holly Tamski – Biomedical Sciences Ph.D. student
Miles Gray – Undergraduate student