Ben Alman for Giving
Principal Investigator
James R. Urbaniak, M.D., Distinguished Professor of Orthopedic Surgery
Professor of Orthopaedic Surgery
Chair of Orthopaedic Surgery
Professor in Neurosurgery
Professor in Pharmacology and Cancer Biology
Professor in the Department of Pathology
Professor in Pediatrics
Professor in Cell Biology
Co-Director of the Duke Regeneration Center
Member of the Duke Cancer Institute
Contact Information

ben.alman@duke.edu
919 613 6935
308 Research Dr., LSRC B330A
Durham, NC

Home

Ben Alman, MD, is an orthopaedic clinician-scientist whose research focuses on understanding the role of developmentally essential 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 extensively uses genetically modified mice to model human disease. He used this approach to identify new drug therapies for musculoskeletal tumors and improve the outcome of related cartilage, skin, and bone processes. 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 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. He has more than 175 peer-reviewed publications in journals such as Lancet, Cell, and Nature Medicine. He 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 percent of desmoid tumors. Based on this work, ß-catenin analysis is used to diagnose 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 and 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, he found that factors from the blood of juvenile animals can rejuvenate fracture repair.

Dr. Alman and his research team identified the first mutation causing enchondromas (a benign pre-malignant cartilage tumor). 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 treat sarcomas.

Research

We are using cell and developmental biology to identify & improve therapeutic approaches to regeneration & pathologic disorders.

Wound Healing
Stem Cells & Neoplasia
Cartilage & Joint Development
Joint Degeneration
Bone Regeneration

Wound Healing

The entire wound-healing process is a complex series of events that begins at the moment of injury and can continue for months to years. Our goal is to determine the role of the Wnt pathway, particularly its key molecule β-catenin, in the reconstitution of the skin's epithelial and dermal components during wound healing. Using different genetically engineered mice designed in our lab, we investigate the fate of the cells contributing to healing and the role of β-catenin in this process. As part of this work, we identified a novel drug that can decrease scar size and is working to determine how it can be developed into a topical agent for patients. 

Team Members: Puviindran Nadesan, Heather Whetstone, Saeid Amini Nik, Kirsten Bielefeld and Raymond Poon.

Stem Cells & Neoplasia

Stem cells are the earliest step in the hierarchal progressive maturation to functionally differentiated cells with self-renew and fast proliferation characteristics. Although the concept that tumors contain a subpopulation of cells with stem cell properties has been demonstrated in several tumor types, little has been reported on the role of stem cells in musculoskeletal (MSK) tumors, perhaps due to lack of unique mesenchymal stem cell (MSC) marker. Our studies hypothesize that MSK tumors contain a subpopulation of tumor-initiating cells. The first step in our research is identifying and isolating tumor-initiating cells (TIC) from musculoskeletal tumors. Further study of this population of cells will allow for the characterization of molecular pathways regulating the development of MSK, ultimately identifying potential novel therapeutic targets. We are also studying the role of developmentally important signaling pathways in fibrous and cartilaginous tumors (aggressive fibromatosis, desmoid tumors, enchondromas, and chondrosarcoma). In this work, we generated genetically modified mice that developed these tumors. We are studying how modulating the signaling pathways causes these tumors and how this information could be used to develop potential new therapeutic approaches.

Team Members: Hirata Makoto, Peter Dixon, Qingxia Wei, Mushriq Al Jazrawe, Cassandra Tyson, Ronak Ghanbari-Azarnier, Shingo Sato, and Katherine Ho.

Cartilage & Joint Development

During development, cell fate experiments have determined that growth plate and articular chondrocytes differentiate from two distinct populations of cells. Within the growth plate, the Indian hedgehog (Ihh) regulates chondrocyte proliferation and differentiation that involves a feedback loop with the parathyroid hormone-related protein (PTHrP). We have generated transgenic mice showing that deregulation of the hedgehog/PTHrP feedback loop during growth plate development results in chondrodysplasias and the development of cartilage tumors; however, the role of hedgehog signaling in the differentiation and maintenance of articular chondrocyte progenitors is poorly defined. Through investigation of transgenic mice, we hope to identify further the role of hedgehogs and other signaling pathways on growth plate and articular cartilage development.

Team Members: Heather Whetstone, Jason Rockel, Claire Hsu, and Louisa Ho.

Joint Degeneration & Repair

Osteoarthritis (OA) is a degenerative disease of the joints, characterized by degradation and calcification of articular cartilage and subchondral bone changes. Because articular cartilage does not regenerate, understanding how joints develop may provide new insight and novel therapies for OA. Our current data suggests that Wnt, Hh, sterols, and other signaling pathways involved in normal joint development may also be involved in the development and progression of OA. Therefore, we aim to elucidate how modulating these pathways can attenuate OA pathology and enhance joint repair. 

Team Members: Henry Ma, Amanda Ali, Heather Whetstone, and Peter Kannu.

Bone Regeneration

Endochondral ossification is recapitulated during long bone repair. Although the β-catenin pathway has been investigated in bone development and skeletogenesis context, its role in bone regeneration is unclear. Using pharmacological reagents, we can augment β-catenin signaling during bone repair and have observed substantially improved healing in various pathological conditions. Deficiencies seen in bone regeneration with age are (in part) mediated by the β-catenin pathway. Our models, which can “rejuvenate” aged bone regeneration, do so in a β-catenin dependent manner. Mutation in the FGFR3 gene (achondroplasia) results in augmented bone repair and cellular differentiation. We are currently investigating the impact of FGFR3 signaling on osteoblast differentiation. Furthermore, we are also investigating how glucocorticoids induce osteoporosis in chronic pediatric diseases such as Acute Lymphoblastic Leukemia and Duchene Muscular Dystrophy. Insights into these pathways and diseases may offer new therapeutic options to enhance bone regeneration or fracture repair. 

Team Members: Puviindran Nadesan, Linda Vi, Farasat Zaman, Gurpreet Baht, Saber Ghadakzadeh, Heather Whetstone, Chunying Yu and Simon Kelley.

People

The Alman laboratory research focuses on five research projects: Wound Healing, Stem Cells and Neoplasia, Cartilage and Joint Development, Joint Degeneration and Repair, and Bone Regeneration. Members within the five research projects interact extensively and share and complement research expertise.

Director, Research Operations and Administration
Graduate Student
Research Analyst II
Postdoctoral Associate
Graduate Student
Graduate Student
Research Analyst II
Postdoctoral Associate
Graduate Student
Research Analyst II
Postdoctoral Associate
Graduate Student
Graduate Student
Visiting Research Scholar

Publications

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Selected Publications

Publications
Book Sections
Conference Papers
Journal Articles

*Due to sponsor publicity restrictions, some awards may not be displayed.

Publications

Book Sections

Conference Papers

Journal Articles

Research Opportunities

Alman job opps


Dr. Alman is always looking to supervise enthusiastic graduate students and post-docs.

Individuals interested in any of his ongoing projects or who desire to build off of his expertise to explore related research areas are encouraged to contact him.

News and Events

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Celebrations

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Friends, Mentors, and Peers Supporting Each Other

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Alman Lab Welcome BBQ