The Core Center for Musculoskeletal Biology & Medicine (CCMBM) defines itself by emphasizing musculoskeletal-specific education and services that are critical to its members but not available elsewhere in the university system | |
Musculoskeletal diseases are the 2nd most common cause of disease burden. These include common conditions like osteoporosis and fractures, but also rare conditions that cause bony deformities and structural weakness. Fibrous dysplasia/McCune-Albright Syndrome (FD/MAS) is a debilitating disease for which there are no directed treatments available. FD/MAS is a somatic, mosaic genetic disease caused by a mutation in GNAS, which encodes the Gs-alpha protein. This mutation causes constitutive activation of the Gs-GPCR signaling pathway in affected tissues. When the GNAS mutation is expressed in the skeleton, fibrotic, expansile bone lesions form, causing disfigurement, fractures and chronic pain. There are currently no FDA-approved medical therapies designated for FD, and identifying therapies to manage this disease has been extremely challenging. There is an urgent need to find treatments that can target the underlying fibrotic pathology. Since the pathways that cause FD/MAS are also the same pathways that control bone formation, finding therapies for FD/MAS would also allow us to improve the development of treatments for fractures and osteoporosis. | |
Figure 1. Radiologic imaging of fibrous dysplastic bone. Left) Craniofacial CT scan of a 33 year old female with FD/MAS, showing extensive fibrous dysplastic bone in the skull (representative lesions, red arrows). Narrowing of the optic canal can be seen in this image (yellow arrow). In addition, this craniofacial lesion shows cystic changes that can be seen in some FD lesions. Right) FD of the right tibia as seen on plain film X ray, of the same patient at age 29. | |
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Earlier this month, the inaugural cohort of STRETCH scholars met with CCMBM staff and UC LEADS representatives to officially launch their research projects.
The STRETCH program stimulates collaboration among scientists by supporting students throughout a two-year research experience that incorporates two academic years and one summer of research at the home campus, and a second summer of research at another UC.
Learn more about the program here.
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STRETCH SCHOLAR
Phiphi Dinh
Department of Bioengineering, UC Riverside
"Noninvasive Assessment of Tendon Mechanics for Grip Rehabilitation"
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STRETCH SCHOLAR
Kaajal Sharma
Department of Cell Biology and Neuroscience, UC Riverside
“Structural and Functional Integration of the Neuromusculoskeletal System”
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Musculoskeletal Science Without Borders: Towards Health Equity
Mark your calendars for the CCMBM/Department of Orthopaedic Surgery Spring Scientific Retreat scheduled for March 18-19, 2025. Location will be at UCSF Mission Bay Campus, Genentech Hall. Event details will be forthcoming as we draw closer to the retreat.
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Chiho Kadota-Watanabe, DDS, PhD
Postdoctoral Scholar
Department of Orofacial Sciences
Award: JIC Grant Development Award
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Hiroyori Fusagawa, MD
Postdoctoral Fellow
Orthopaedic Surgery
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Kristine Godziuk, PhD
Assistant Professor
Physical Therapy & Rehabilitation Science
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Dustin Snapper, MD, MS
Specialist
Orthopaedic Surgery
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Viviana Hermosilla Aguayo, PhD
Postdoctoral Scholar
Orthopaedic Surgery
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Zhenmeiyu Li, PhD
Postdoctoral Researcher
Neurosurgery
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Identification of Alzheimer’s disease (AD) onset risk can facilitate interventions before irreversible disease progression. We demonstrate that electronic health records from the University of California, San Francisco, followed by knowledge networks (for example, SPOKE) allow for (1) prediction of AD onset and (2) prioritization of biological hypotheses, and (3) contextualization of sex dimorphism. We trained random forest models and predicted AD onset on a cohort of 749 individuals with AD and 250,545 controls with a mean area under the receiver operating characteristic of 0.72 (7 years prior) to 0.81 (1 day prior). We further harnessed matched cohort models to identify conditions with predictive power before AD onset. Knowledge networks highlight shared genes between multiple top predictors and AD (for example, APOE, ACTB, IL6 and INS). Genetic colocalization analysis supports AD association with hyperlipidemia at the APOE locus, as well as a stronger female AD association with osteoporosis at a locus near MS4A6A. We therefore show how clinical data can be utilized for early AD prediction and identification of personalized biological hypotheses. | |
Figure 1: a, From the UCSF EHRs and the UCSF Memory and Aging Center (MAC) database, participant and clinical information was extracted, filtered and prepared for time points before the index time. All clinical features extracted were one-hot encoded and trained on random forest (RF) models to predict future risk of AD diagnosis. Models were evaluated on a 30% held-out evaluation set to compute AUROC/AUPRC and interpreted based on feature importances and using a heterogeneous knowledge network (SPOKE). Top features were then further validated in external databases. b, Filtering a consistent set of individuals with AD and controls from the UCSF EHR for model training and testing. Filtered participant cohorts are shown in Table 1 and split with 30% held-out set for testing. c, Bootstrapped performance of RF models on the held-out evaluation set (n = 300 bootstrapped iterations of 1,000 participants, prevalence of AD on held-out set = 0.003). Bootstrapped AUROC performance for models trained and tested on female strata and male strata are also shown. The box shows quartiles (25th, 50th and 75th percentiles), whiskers extend to 1.5 times the interquartile range, and the remaining points are outliers. | | |
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In an effort to better collect an accurate list of CCMBM member publications, we are asking our members to please alert us to any submitted, accepted, or published manuscripts that either utilized CCMBM funding/core services or resulted from a collaboration with our membership.
Simply complete the our submission form and we will spotlight your publication in a future newsletter and on social media. We are excited to learn about your research!
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We are excited to host the above upcoming seminars and bring speakers to the UCSF community this 2024-2025 academic year. CCMBM members, including junior investigators, trainees and learners, have priority to meet with visiting faculty speakers. The CCMBM Seminar Committee will provide scheduling details as we near each speaker’s visit. Contact Pui Yee Law if you would like us to consider and invite potential speakers to visit UCSF. | | |
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Application Deadline: December 20, 2024, 12:00PM PST
Proposals reviewed and funded on a rolling basis.
CCMBM is pleased to announce the CCMBM Junior Investigator Travel Award, which is intended to support the travel of trainees to develop expertise, network, or acquire skills in a field at a scientific conference that the applicants may otherwise be unable to attend. The award is particularly designed to encourage travel to a conference where the trainee may not be presenting an abstract, but where interactions with other attendees and participation in conference activities can serve as a springboard for trainees to transition to the next stages in their scientific careers.
Travel awards may only be used to cover economy airfare for up to $200 per award and travel to be completed by March 31, 2025.
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Application Deadline: January 6, 2025
Award Notifications: End of January 2025
The UCSF Core Center in Musculoskeletal Biology and Medicine (CCMBM) is accepting applications for its Tools and Technology (T/T) Grant Program. Research topics should be within the musculoskeletal (MSK) field. The goal of this grant mechanism is to encourage members from any UC campus to develop or adopt cutting-edge technologies or computational resources that have yet to be widely used for MSK research. T/T funds will help investigators customize and demonstrate the feasibility of these approaches for MSK-specific research needs.
Priority will be given to early career investigators and to projects that make new protocols available to other CCMBM members through UCSF Cores, including CoLabs and CCMBM Cores.
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The Grant Development Award provides funding for a junior CCMBM member to host a meeting (e.g., lunch or dinner) with 1-3 UCSF faculty members who are outside of the trainee’s current lab to:
1) brainstorm/solicit informal feedback on a study idea or research direction
2) learn about the latest methods and techniques used in related fields
3) identify potential collaborators
4) promote inter-disciplinary MSK research
5) expand the trainee’s professional network
If you are not a member, you may concurrently apply for membership while your Grant Development application is being reviewed.
Apply via the online application form today! Contact Noah Bonnheim for questions on this funding opportunity.
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Recognizing the need for collaboration of MSK scientists with experts outside of the MSK field, we are providing support to MSK Center members to host a meal for a creative and enjoyable in-person networking meeting to stimulate these interactions and to further develop new research ideas and plans to fund them. Faculty, staff, and trainees who are MSKC/CCMBM members are encouraged to apply to host an event.
If you are not a member, you may concurrently apply for membership while your Open MIKE application is being reviewed.
Apply via the online application form today! Contact Cristal Yee for questions on this funding opportunity.
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UCSF Talks is a new resource for anyone interested in learning about the latest seminars happening at UCSF. It lists all seminars open to the entire UCSF community including regular seminar series, special seminars, supergroups, and thesis talks. If you would like to receive weekly event listing emails, you can sign up for the USCF Talks Google Group. To add an event to the website, please contact Jon Zhang. | |
Core Center for Musculoskeletal Biology and Medicine (CCMBM), 513 Parnassus Avenue, S-1161, San Francisco, CA 94143 | | | | |
