Dr. Alman is an orthopaedic clinician-scientist whose research focuses on understanding the role of developmentally important processes in the pathologic process involving the musculoskeletal system. The long-term goal of his work is to use this knowledge to identify improved therapeutic approaches to orthopaedic pathologic disorders. He makes extensive use of genetically modified mice to model human disease, and used this approach to identify new drug therapies for musculoskeletal tumors and to improve the outcome of related processes in cartilage, skin, and bone. As part of this work, Dr. Alman generated novel genetically modified mice to study tumors and reparative processes and is using these to develop new therapies. He also works on cellular heterogeneity in bone tumors, such as sarcomas, and how this relates to developmental processes. His lab identified a subpopulation of tumor initiating cells in musculoskeletal tumors, and found that this subpopulation of is responsible for sarcoma self-renewal.
Another focus of the Alman Lab is to determine the regulation of mesenchymal cells in repair processes. Dr. Alman’s work on beta-catenin (ß-catenin) using transgenic mice was the first demonstration of the importance of this pathway in fracture repair. More recently, he used lineage-tracing studies to investigate the role of macrophage cells in skin and bone repair, and found a novel role for young hematopoietic cells in rejuvenating fracture repair.
Dr. Alman is the principal investigator on several NIH grants; has more than 175 peer reviewed publications in journals such as Lancet, Cell, and Nature Medicine; and has supervised over 30 graduate students and postdoctoral research trainees in his lab. He was recruited to Duke from Toronto’s Hospital for Sick Children in 2013.
Dr. Alman identified somatic mutations resulting in ß-catenin mediated transcription in more than 70% of desmoid tumors. Based on this work, ß-catenin analysis is used to diagnosis this tumor type, and mutational analysis is used as a prognostic test.
Dr. Alman’s group found that ß-catenin mediated transcription is activated during the proliferative phase of wound healing and regulates scar size, as well as osteoblast differentiation in fracture repair. He was the first to show that circulating factors regulate fracture healing and ß-catenin during repair, and using parabiosis, found that factors from the blood of juvenile animals can rejuvenate fracture repair.
The first mutation causing enchondromas (a benign pre-malignant cartilage tumor) was identified by Dr. Alman and his research team. Using a mouse expressing the mutation, he identified pathways regulating tumor progression.
Dr. Alman and his group were the first to show that mesenchymal tumors contain a subpopulation of cells with tumor propagating characteristics and that targeting this cell population can be used to treat sarcomas.
- Identification of properties of tumor proagating cells that can be therapeutically targeted in mouse and human sarcomas
- Use of genetically modified mice to determine how novel members in the hedgehog-signaling cascade regulate bone development, growth, cartilaginous neoplasia and the development of osteoarthritis
- Study of interactions between hematopoietic and mesenchymal cells, and the role of novel proteins involved in this interaction in bone and cartilage development, repair, and the rejuvenation of fracture healing
- Discovery of novel therapies for desmoid tumor, a mesenchymal tumor also called aggressive fibromatosis, using cell culture and genetically modified mice
Selected Publications & Grants
Zhang, Hongyuan, Vijitha Puviindran, Puviindran Nadesan, Xiruo Ding, Leyao Shen, Yuning J. Tang, Hidetoshi Tsushima, et al. “Distinct Roles of Glutamine Metabolism in Benign and Malignant Cartilage Tumors With IDH Mutations.” J Bone Miner Res 37, no. 5 (May 2022): 983–96. https://doi.org/10.1002/jbmr.4532.More info
Yahara, Yasuhito, Tuyet Nguyen, Koji Ishikawa, Katsuhiko Kamei, and Benjamin A. Alman. “The origins and roles of osteoclasts in bone development, homeostasis and repair.” Development 149, no. 8 (April 15, 2022). https://doi.org/10.1242/dev.199908.More info
Schut, Anne-Rose W., Anne L. M. Vriends, Andrea Sacchetti, Milea J. M. Timbergen, Benjamin A. Alman, Mushriq Al-Jazrawe, Dirk J. Grünhagen, Cornelis Verhoef, Stefan Sleijfer, and Erik A. C. Wiemer. “In desmoid-type fibromatosis cells sorafenib induces ferroptosis and apoptosis, which are enhanced by autophagy inhibition.” Eur J Surg Oncol, February 19, 2022. https://doi.org/10.1016/j.ejso.2022.02.020.More info
Naert, Thomas, Dieter Tulkens, Tom Van Nieuwenhuysen, Joanna Przybyl, Suzan Demuynck, Matt van de Rijn, Mushriq Al-Jazrawe, et al. “CRISPR-SID: Identifying EZH2 as a druggable target for desmoid tumors via in vivo dependency mapping.” Proc Natl Acad Sci U S A 118, no. 47 (November 23, 2021). https://doi.org/10.1073/pnas.2115116118.More info
Tang, Yuning Jackie, Vijitha Puviindran, Yu Xiang, Yasuhito Yahara, Hongyuan Zhang, Puviindran Nadesan, Yarui Diao, David G. Kirsch, and Benjamin A. Alman. “Tumor-propagating side population cells are a dynamic subpopulation in undifferentiated pleomorphic sarcoma.” Jci Insight 6, no. 22 (November 22, 2021). https://doi.org/10.1172/jci.insight.148768.More info
Rickert, Kathleen D., Paolo Arrigoni, Camille R. Guzel, Helena F. Barber, Benjamin A. Alman, and Robert K. Lark. “Growth Modulation by Stimulating the Growth Plate: A Pilot Study.” Ultrasound Med Biol 47, no. 8 (August 2021): 2339–45. https://doi.org/10.1016/j.ultrasmedbio.2021.03.036.More info
Pathmanapan, Sinthu, Olga Ilkayeva, John T. Martin, Adrian Kwan Ho Loe, Hongyuan Zhang, Guo-Fang Zhang, Christopher B. Newgard, Jay S. Wunder, and Benjamin A. Alman. “Mutant IDH and non-mutant chondrosarcomas display distinct cellular metabolomes.” Cancer Metab 9, no. 1 (March 24, 2021): 13. https://doi.org/10.1186/s40170-021-00247-8.More info
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Kavolus, Joseph J., Alexander L. Lazarides, Christina Moore, Thorsten M. Seyler, Samuel S. Wellman, David E. Attarian, Michael P. Bolognesi, and Benjamin A. Alman. “The Calpain Gene is Correlated With Metal-on-Metal Hip Replacement Failures.” J Arthroplasty 36, no. 1 (January 2021): 236-241.e3. https://doi.org/10.1016/j.arth.2020.07.054.More info
Alman, Benjamin, and Gurpreet Baht. “Parabiosis: Assessing the Effects of Circulating Cells and Factors on the Skeleton.,” 2230:105–13, 2021. https://doi.org/10.1007/978-1-0716-1028-2_7.More info
- Training Program in Developmental and Stem Cell Biology (Mentor), awarded by National Institutes of Health, administered by Basic Science Departments, 2001-2027 More info
- Resorbable, Phsophorylated Poly(ester urea) Surgical Adhesive to Enhance Fracture Healing (Advisor), awarded by National Institutes of Health, administered by Trauma, Acute, and Critical Care Surgery, 2021-2026 More info
- Targeting the metastasis initiating cell in undifferentiated pleomorphic sarcoma (Principal Investigator), awarded by National Institutes of Health, administered by Orthopaedics, 2021-2026 More info
- The role of macrophage subpopulations in the rejuvenation of fracture repair (Principal Investigator), awarded by National Institutes of Health, administered by Orthopaedics, 2021-2025 More info
- Exercise Induced Muscle Secreted Factors That Modify Osteoarthritis (OA) Severity (Principal Investigator), awarded by National Institutes of Health, administered by Orthopaedics, 2021-2023 More info
- Duke CTSA (TL1) Year 5 (Mentor), awarded by National Institutes of Health, administered by Institutes and Centers, 2018-2023 More info
- Cabinet Radiation Therapy System for Small Animals (Major User), awarded by North Carolina Biotechnology Center, administered by Radiation Oncology, 2022-2023 More info
- Genetic approaches to skin regeneration in zebrafish (Co-Mentor), awarded by National Institutes of Health, administered by Surgery, Plastic, Maxillofacial, and Oral Surgery, 2020-2023 More info
- Exercise-induced recovery of intervertebral disc health (Mentor), awarded by National Institutes of Health, administered by Orthopaedics, 2020-2022 More info
- Translational Research in Surgical Oncology (Mentor), awarded by National Institutes of Health, administered by Surgery, Surgical Sciences, 2002-2022 More info
- Benjamin A. Alman, MD, Principal Investigator
- Puviindran Nadesan, Research Analyst
- Jackie Tang, Graduate Student
- Hidetoshi Tsushima, Postdoctoral Researcher
- Claire Hsu, Postdoctoral Researcher
- Vijitha Puviindran, Research Analyst
- Terese Camp, Shared Resource Lab Manager
- Gurpreet Baht, Postdoctoral Researcher
- Farhat Ghaznawi, Postdoctoral Researcher
- Linda Vi, Graduate Student
Dr. Alman is always looking to supervise enthusiastic graduate students and post-docs. Individuals with interests in any of his ongoing projects, or with a desire to build off of his expertise to explore related areas of research, are encouraged to contact him.
Duke Hospital South, 200 Trent Drive, Orange Zone 5th floor
DUMC 2888, Durham, NC 27710