Clifford J. Rosen, MD

Faculty Scientist III
Associate Director, Center for Clinical & Translational Science
Co-Principal Investigator of the Northern New England CTR Network

Carolyn Chlebek, PhD

Postdoctoral Fellow
Carolyn.Chlebek@mainehealth.org

Postdoctoral Fellow Carolyn Chlebek is interested in understanding the influence of bioenergetic cellular activity on bone health. Using the therapeutic canagoliflozin, she restricts systemic glucose availability in mice. In humans, canagliflozin is associated with increased risk of fracture, despite the lack of receptors expressed in bone cells. In the Rosen lab, we are also using diet interventions and in vitro studies to determine the role of bioenergetic pathways in bone function. We hypothesize that metabolic pathways directly influence bone quality in health and disease.

Samantha Costa, BS

PhD Candidate
Samantha.Costa@mainehealth.org

Samantha Costa has been investigating the potential dual inhibitory and stimulatory mechanism of programmed death-ligand 1 (PD-L1) expressing myeloid cells in obese mice. PD-L1 is an immune checkpoint protein that functions as an immune response “brake” when it interacts with the program death-1 (PD-1) receptor. Ms. Costa’s findings challenge the current paradigm that obesity is an inflammatory disease, by demonstrating diet-induced obesity leads to immunosuppression within the bone marrow, which is a key microenvironment for systemic immune/inflammatory regulation. Her data show bone marrow myeloid cells have aberrant increased expression of PD-L1 after diet-induced obesity. In addition, Ms. Costa’s findings suggest obesity-related bone loss to be coupled with PD-1/PD-L1 mediated osteoclastogenesis, indicated by trabecular and cortical bone loss, increased PD-1-expressing osteoclast precursors, and increased tartrate-resistant acid phosphatase (TRAP) expressing mature osteoclasts. The outcomes of Ms. Costa’s research will offer insight into obesity-related immune impairment and associated bone loss while providing a foundation for continued research in immune therapies for non-tumor-bearing obese individuals.

Jennifer Daruszka, BS

Research Assistant III
Jennifer.Daruszka@mainehealth.org

Jennifer’s work involves taking care of animal colonies and performing genotyping for identification. She assists Victoria DeMambro in the Physiology Core in scanning mice using Faxitron/DEXA and NMR for their body composition and bone phenotype. Additionally, she trains people on how to use these machines so they can scan their own strains of mice. She also helps set up and breakdown the metabolic cages for the Physiology Core performing mouse runs on Institutional studies for research.

Victoria E. DeMambro, MS

Physiology Core Manager and PhD Candidate
Victoria.DeMambro@mainehealth.org

Victoria is the manager of the Maine COBRE in Metabolic Networks Physiology CORE providing in vivo and in vitro metabolic phenotyping and data analysis for COBRE-supported, MHIR and outside investigators. She is also a PhD candidate at the University of Maine at Orono, in Graduate School of Biomedical Science and Engineering (GSBSE) studying in the labs of Dr. Guntur and Rosen. Her main research focus is on Hypophosphatasia (HPP), a rare bone disease resulting in rickets, osteomalacia, bone fragility, chronic fatigue and muscle weakness. HPP occurs due to mutations in the Alpl gene coding for the Tissue Non-Specific Alkaline Phosphatase protein (TNAP) a known pro-mineralizing enzyme. Her research interests involve HPP phenotypes beyond known bone defects and is currently investigating the role of TNAP in lipid accumulation and mitochondrial dynamic processes.

Eben Estell, PhD

Staff Scientist
Eben.Estell@mainehealth.org

Dr. Estell’s research in the Rosen Lab focuses on the mechanisms of bone adaptation to physical load, investigating how the interplay between chemical and mechanical stimuli generated during exercise direct cellular function. His current project investigates the role of irisin, a signaling protein released from muscle during exercise, in regulating osteoclast differentiation and osteocyte mechanotransduction during the remodeling response of bone to exercise.

Tsunagu Ichikawa, BS

Medical Student at the University of New England

Moving from previous work in Management Consulting towards an interest in both the clinical and basic science aspects of healthcare, Tsunagu is a medical student at the University of New England College of Osteopathic Medicine who has joined the Rosen lab to work with Dr. Estell on studies investigating the role of irisin in bone homeostasis and disease. Pursuing an interest in orthopedics, he will focus on mouse models for surgical induction of osteoarthritis to assess the role of irisin in protecting bone and cartilage during progression of this degenerative disease.

Phuong Le, MS

Scientific Manager III
Phuong.Le@mainehealth.org

Besides managing day-to-day operations of Dr. Rosen’s lab, Phuong’s research work has been examining how Zinc finger protein 467 (Zfp467) plays a role in the regulation of thermogenesis in adipocytes. Zfp467 is a novel regulator of cell fate by inhibiting osteoblast commitment and stimulating adipocyte differentiation; it was found to enhance adipogenic differentiation by upregulating Pparg. Her study explores the genetic loss of Zfp467 and whether or not global deletion of Zfp467 (Zfp467-/-) causes an increase in adipogenesis, enhance beiging/browning of the white adipocytes, or increase in thermogenesis in adipose tissues. Phuong also examines the conditional deletion of Zfp467 in adipose lineage cells by crossing the Adipoq^Cre mice with Zfp467^fl/fl mice to determine their general phenotypes.

Linyi Liu, MS

Visiting Scholar and Doctoral Candidate

Linyi came to our lab from West China School of Stomatology and his work focuses on the effects of caloric restriction on bone and bone marrow using different mouse models. He is also investigating the possible mechanisms responsible for bone-fat balance.

Casey McAndrews, BA

Medical Student at the University of New England

Casey is currently a medical student at the University of New England and is interested in learning more about the effects that bioenergetics have on bone health. In the Rosen lab, she will be assisting in a study involving Canagliflozin (CANA), a widely used therapeutic for the treatment of type II diabetes mellitus and congestive heart failure, which may be associated with decreased bone density and increased risk of bone fracture. Using a mouse model, we hope to further understand how treatment with CANA may lead to impairment of longitudinal bone health.

Erin McFarlane, MS

Medical Student at the University of New England

Erin MacFarlane is a current second year medical student interested in the fields of Orthopedics and Surgery. She completed her M.Sc. in Dr. Jenny Bruin’s lab at Carleton University in 2019, where she investigated the role persistent organic pollutants have on pancreatic development and diabetes pathogenesis using human stem cell models. Erin also worked as a clinical research assistant at the Ottawa Hospital Research Institute, Division of Orthopedic Surgery, prior to starting medical school. Currently, she is working alongside Carolyn Chlebek to understand how canagliflozin, a drug used to treat diabetes, affects bone health and mineralization.

Iana Mizumukai de Araujo, PhD

Visiting Scientist

Iana came to the Rosen Lab from the Ribeirão Preto Medical School, University of São Paulo, Brazil where she is a postdoctoral fellow doing a clinical research with people with anorexia nervosa to understand bone loss in this condition. In the Rosen Lab, she is interested in understanding the effects of 30% of caloric restriction have in bone and bone marrow niches. She uses the mouse strain 11 beta-hydroxysteroid dehydrogenase type 1 (Hsdb11) to study the role of cortisol in bone loss.