Benjamin Alman

Positions:

James R. Urbaniak, M.D., Distinguished Professor of Orthopedic Surgery

Orthopaedics
School of Medicine

Professor of Orthopaedic Surgery

Orthopaedics
School of Medicine

Chair of Orthopaedic Surgery

Orthopaedics
School of Medicine

Professor in Cell Biology

Cell Biology
School of Medicine

Professor in Pediatrics

Pediatrics
School of Medicine

Professor in the Department of Pathology

Pathology
School of Medicine

Core Faculty in Innovation & Entrepreneurship

Duke Innovation & Entrepreneurship
Institutes and Provost's Academic Units

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Co-Director of the Regeneration Next Initiative

Regeneration Next Initiative
School of Medicine

Education:

M.D. 1986

Jefferson Medical College of Thomas Jefferson University

Grants:

Rejuvenating fracture repair: The role of the macrophage and Beta-catenin

Administered By
Orthopaedics
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Stable Isotope Resolved Metabolomics to Interrogate the Interactions between Stroma and Desmoid Tumors

Administered By
Orthopaedics
Role
Principal Investigator
Start Date
End Date

IPA - Janet Prvu Bettger

Administered By
Orthopaedics
Role
Principal Investigator
Start Date
End Date

Collaboration for a Cure: Identifying new Therapeutic Targets for Desmoid Tumors

Administered By
Orthopaedics
Role
Principal Investigator
Start Date
End Date

Targeting Tumor Initiating Cell in Undifferentiated Pleomorphic Sarcoma

Administered By
Orthopaedics
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Publications:

Tracing Tumor Evolution in Sarcoma Reveals Clonal Origin of Advanced Metastasis.

Cellular heterogeneity is frequently observed in cancer, but the biological significance of heterogeneous tumor clones is not well defined. Using multicolor reporters and CRISPR-Cas9 barcoding, we trace clonal dynamics in a mouse model of sarcoma. We show that primary tumor growth is associated with a reduction in clonal heterogeneity. Local recurrence of tumors following surgery or radiation therapy is driven by multiple clones. In contrast, advanced metastasis to the lungs is driven by clonal selection of a single metastatic clone (MC). Using RNA sequencing (RNA-seq) and in vivo assays, we identify candidate suppressors of metastasis, namely, Rasd1, Reck, and Aldh1a2. These genes are downregulated in MCs of the primary tumors prior to the formation of metastases. Overexpression of these suppressors of metastasis impair the ability of sarcoma cells to colonize the lungs. Overall, this study reveals clonal dynamics during each step of tumor progression, from initiation to growth, recurrence, and distant metastasis.
Authors
Tang, YJ; Huang, J; Tsushima, H; Ban, GI; Zhang, H; Oristian, KM; Puviindran, V; Williams, N; Ding, X; Ou, J; Jung, S-H; Lee, C-L; Jiao, Y; Chen, BJ; Kirsch, DG; Alman, BA
MLA Citation
Tang, Yuning J., et al. “Tracing Tumor Evolution in Sarcoma Reveals Clonal Origin of Advanced Metastasis..” Cell Rep, vol. 28, no. 11, Sept. 2019, pp. 2837-2850.e5. Pubmed, doi:10.1016/j.celrep.2019.08.029.
URI
https://scholars.duke.edu/individual/pub1368140
PMID
31509746
Source
pubmed
Published In
Cell Reports
Volume
28
Published Date
Start Page
2837
End Page
2850.e5
DOI
10.1016/j.celrep.2019.08.029

Intracellular cholesterol biosynthesis in enchondroma and chondrosarcoma.

Enchondroma and chondrosarcoma are the most common benign and malignant cartilaginous neoplasms. Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) are present in the majority of these tumors. We performed RNA-seq analysis on chondrocytes from Col2a1Cre;Idh1LSL/+ animals and found that genes implied in cholesterol synthesis pathway were significantly upregulated in the mutant chondrocytes. We examined the phenotypic effect of inhibiting intracellular cholesterol biosynthesis on enchondroma formation by conditionally deleting SCAP (sterol regulatory element-binding protein cleavage-activating protein), a protein activating intracellular cholesterol synthesis, in IDH1 mutant mice. We found fewer enchondromas in animals lacking SCAP. Furthermore, in chondrosarcomas, pharmacological inhibition of intracellular cholesterol synthesis significantly reduced chondrosarcoma cell viability in vitro and suppressed tumor growth in vivo. Taken together, these data suggest that intracellular cholesterol synthesis is a potential therapeutic target for enchondromas and chondrosarcomas.
Authors
Zhang, H; Wei, Q; Tsushima, H; Puviindran, V; Tang, YJ; Pathmanapan, S; Poon, R; Ramu, E; Al-Jazrawe, M; Wunder, J; Alman, BA
MLA Citation
Zhang, Hongyuan, et al. “Intracellular cholesterol biosynthesis in enchondroma and chondrosarcoma..” Jci Insight, vol. 5, Apr. 2019. Pubmed, doi:10.1172/jci.insight.127232.
URI
https://scholars.duke.edu/individual/pub1387942
PMID
31039139
Source
pubmed
Published In
Jci Insight
Volume
5
Published Date
DOI
10.1172/jci.insight.127232

The Fourth Year of Medical School: Time for Reassessment: AOA Critical Issues.

Most U.S. medical schools follow the 4-year model, consisting of 2 preclinical years, core clinical experience, and a fourth year intended to permit students to increase clinical competency, to explore specialty areas, and to transition to residency. Although the design and delivery of Years 1 through 3 have evolved to meet new challenges and expectations, the structure of Year 4 remains largely unchanged. For most students considering a career in orthopaedics, Year 4 is a series of elective rotations in which educational objectives become secondary to interviewing for residency programs. Most accreditation bodies recognize the importance of attainment of competency over the duration of medical school as the goal of educating physicians, and thus, there is a growing interest in reexamining the traditional medical school curriculum with the goal of integrating the final phases of undergraduate education and the first phases of postgraduate education.A literature search was undertaken to identify publications on the duration of medical education. Pilot approaches to competency-based integration of undergraduate medical school and postgraduate training in orthopaedic surgery were reviewed.There have been few data suggesting that 4 years of medical education is superior to shorter-duration programs. Three approaches to competency-based integration of undergraduate medical school and postgraduate training are presented. Their goal is to use student and faculty time more effectively. Each approach offers the opportunity to lower the cost and to decrease the time required for Board Certification in Orthopaedic Surgery. Two approaches shorten the entire duration of medical school and graduate training by using various proportions of the fourth year to begin residency, and one approach expands the duration of orthopaedic training by starting in the fourth year of medical school and including training equivalent to a fellowship program into the residency experience.The effectiveness of such programs will form the basis for revisions to the current orthopaedic training paradigm, resulting in a more effective, efficient, and integrated orthopaedic training curriculum.
Authors
Alman, BA; Purtill, JJ; Pellegrini, VD; Scoles, P
MLA Citation
Alman, Benjamin A., et al. “The Fourth Year of Medical School: Time for Reassessment: AOA Critical Issues..” J Bone Joint Surg Am, vol. 99, no. 13, July 2017. Pubmed, doi:10.2106/JBJS.16.01094.
URI
https://scholars.duke.edu/individual/pub1264995
PMID
28678133
Source
pubmed
Published In
J Bone Joint Surg Am
Volume
99
Published Date
Start Page
e72
DOI
10.2106/JBJS.16.01094

Macrophages promote osteoblastic differentiation in-vivo: implications in fracture repair and bone homeostasis.

Macrophages are activated in inflammation and during early phases of repair processes. Interestingly, they are also present in bone during development, but their function during this process is unclear. Here, we explore the function of macrophages in bone development, growth, and repair using transgenic mice to constitutively or conditionally deplete macrophages. Depletion of macrophages led to early skeletal growth retardation and progressive osteoporosis. By 3 months of age, macrophage-deficient mice displayed a 25% reduction in bone mineral density and a 70% reduction in the number of trabecular bone compared to control littermates. Despite depletion of macrophages, functional osteoclasts were still present in bones, lining trabecular bone and the endosteal surface of the cortical bone. Furthermore, ablation of macrophages led to a 60% reduction in the number of bone marrow mesenchymal progenitor cells and a decrease in the ability of these cells to differentiate to osteoblasts. When macrophages were depleted during fracture repair, bone union was impaired. Calluses from macrophage-deficient animals were smaller, and contained less bone and more fibrotic tissue deposition. Taken together, this shows that macrophages are crucial for maintaining bone homeostasis and promoting fracture repair by enhancing the differentiation of mesenchymal progenitors.
Authors
Vi, L; Baht, GS; Whetstone, H; Ng, A; Wei, Q; Poon, R; Mylvaganam, S; Grynpas, M; Alman, BA
MLA Citation
Vi, Linda, et al. “Macrophages promote osteoblastic differentiation in-vivo: implications in fracture repair and bone homeostasis..” J Bone Miner Res, vol. 30, no. 6, June 2015, pp. 1090–102. Pubmed, doi:10.1002/jbmr.2422.
URI
https://scholars.duke.edu/individual/pub1053523
PMID
25487241
Source
pubmed
Published In
J Bone Miner Res
Volume
30
Published Date
Start Page
1090
End Page
1102
DOI
10.1002/jbmr.2422

Patient outcomes in the operative and nonoperative management of high-grade spondylolisthesis in children.

BACKGROUND: The optimal management of high-grade spondylolisthesis in the growing child is controversial. Some authors have advocated for surgery in all cases regardless of symptoms. Surgical intervention results in a >10% risk of complications with increased risk of neurological injury associated with slip reduction maneuvers. There is a paucity of literature regarding nonoperative management in this setting. This study sought to obtain outcome measures in pediatric patients with high-grade spondylolisthesis managed either operatively or nonoperatively. METHODS: Database review was performed to identify patients with a high-grade (Meyerding grade III to V) spondylolisthesis managed either operatively or nonoperatively. Retrospective radiographic and chart review was performed. Patients were then contacted by phone to obtain current quality-of-life measurements using the Scoliosis Research Society (SRS)-30 questionnaire. RESULTS: Fifty-three patients were identified for inclusion in the study and 49 were contacted for 92% follow-up. Twenty-four patients were treated with operative intervention, and 25 patients were initially treated nonoperatively, but 10 went on to require surgical intervention. Mean age at presentation was 12.6 years (range, 8 to 17 y) and mean age at follow-up was 20.1 years (range, 10 to 29 y). There were no outcome differences between the groups. A more kyphotic slip angle was associated with worse SRS-30 outcome scores across all groups. In the nonoperative group, the slip angle was significantly larger in patients who failed conservative treatment (34 ± 17 degrees) than in those who remained nonsurgical at final follow-up (20 ± 14 degrees). Slip angle in the operative group was 27 ± 14 degrees. In surgical patients, an older age at surgery was associated with better SRS-30 outcome scores. CONCLUSIONS: Nonoperative management or "watchful waiting" of the minimally symptomatic or asymptomatic child with a high-grade spondylolisthesis is safe and does not lead to significant problems. Operative intervention for the symptomatic patient achieves similar long-term results compared with patients whose minimal symptoms do not warrant surgery. Delayed surgical intervention does not result in worse outcomes. Regardless of treatment modality, patients with a more kyphotic slip angle tend to have a poorer prognosis. LEVEL OF EVIDENCE: Level III.
Authors
Lundine, KM; Lewis, SJ; Al-Aubaidi, Z; Alman, B; Howard, AW
MLA Citation
Lundine, Kristopher M., et al. “Patient outcomes in the operative and nonoperative management of high-grade spondylolisthesis in children..” J Pediatr Orthop, vol. 34, no. 5, July 2014, pp. 483–89. Pubmed, doi:10.1097/BPO.0000000000000133.
URI
https://scholars.duke.edu/individual/pub1028597
PMID
24590330
Source
pubmed
Published In
J Pediatr Orthop
Volume
34
Published Date
Start Page
483
End Page
489
DOI
10.1097/BPO.0000000000000133