Category: Research

Michael Geisman Fellowship Grant

The Michael Geisman Fellowship Grant program awards funding to post-doctoral trainees who are currently working on projects with clear relevance to osteogenesis imperfecta (OI), or who have projects that will enable them to develop expertise in OI research.

Applicant Requirements:

• Applicant must hold an MD, DDS, DO, or PhD, and be appointed at the level of a post-doctoral trainee, or equivalent, within an academic institution.
• Applicant should have completed their Ph.D. or clinical training within the past five (5) years.

Fellowship Guidelines:

• Michael Geisman Fellowship awards provide up to $50,000 per year. It is the intention of the OI Foundation that grant monies be used to fund actual costs related to the research being performed including Fellow salary, fringe benefits, and supplies.
• Fellowship awards are for one year; a second year of funding may be approved based upon satisfactory performance during the first year of funding.
• Research must be done under the supervision of mentor with training and experience in osteogenesis imperfecta research or research in a related field.

How to Apply:

1. Complete application (pg. 2-8)
2. Mentor of applicant must submit a copy of his/her NIH biosketch and a letter of recommendation on behalf of the trainee, which also confirms that the mentor will supervise the trainee’s research.
3. Applications require two additional letters of recommendation from scientists or clinicians who can comment upon the applicant’s training, ability, and potential to develop expertise in OI research.
4. Submit application, reference letters, and mentor biosketch as PDF documents to sconnors@oif.org NO LATER THAN November 30, 2022.

If you have any questions, please contact Stacie Connors at sconnors@oif.org.

Click here for the 2022 Michael Geisman Fellowship application.

Move OI Research Forward – Participate in OI Studies

A clinical study is research that involves human volunteers and seeks to answer questions that will add to our knowledge about a medical condition or how to treat it. Learn more about types of studies, how they are organized, and what to consider before participating by reviewing the OIF’s What You Need To Know About Clinical Trials factsheet.

All current OI Studies are listed on the OIF’s Current Studies webpage at www.oif.org/currentstudies.

The OI Foundation would like to bring your attention to current OI research studies:

ORBIT Study

The Ultragenyx ORBIT study is investigating a new treatment in pediatric and young adults with OI Types I, III, or IV. You can find more information on the study flyer here.

If you are interested in learning more about this trial or would like to see if you are able to participate, please reach out to Erin at trialrecruitment@ultragenyx.com

OI Wellbeing Study

OI Community Members Ages 13-17: Participate in the OI Wellbeing Study!
In partnership with the OIF, researchers at Baylor College of Medicine are conducting a study to better understand the mental health and pain experiences of the OI community. You will have the opportunity to share your individual experiences and discuss what you think could be improved for people living with OI. Your feedback will inform future research in this area.

Taking part in the study includes participating in an approximately one-hour online interview and the completion of a questionnaire, for which you will be compensated $50. This study is for US residents only. If you or your child are interested in participating in the study, please contact the study team at OIWellbeing@bcm.edu for more information.

Use of clear aligners for the treatment of dental malocclusion in individuals with Osteogenesis Imperfecta Types III and IV

The purpose of this study is to determine if it is safe to use Invisalign clear aligners in correcting the misalignment of teeth in people with OI. Clear aligners are transparent plastic trays that are designed to fit over your teeth. With each new tray, teeth are moved a little at a time until they reach the desired position.

For more information, or to see if you are eligible to participate, please contact: Dianne Nguyen, BBDC Project Manager at (713)798-6694 or diannen@bcm.edu

Longitudinal Study of Osteogenesis Imperfecta

The Brittle Bone Disorders Consortium is currently recruiting for a Longitudinal Study of Osteogenesis Imperfecta. The purpose of this natural history study is to perform a long-term follow-up of a large group of people with osteogenesis imperfecta (OI). We will collect information including medical history, number of broken bones, surgeries done, medications taken, ability to walk, pain, lung function and breathing, hearing, and bone mineral density.

The overall goal is to improve the health and quality of life of people with OI. Click here to learn more about this study.

Join the OI Registry! The easiest way to learn more about current and upcoming clinical studies is to enroll in the OI Registry. Once you enter your information into this registry, the OIF or researchers will have access to your deidentified information and may ask you to participate in OI surveys or studies. Click here to join now.

This month, the Brittle Bone Disorders Consortium was featured as the Consortium Spotlight by the Rare Diseases Clinical Research Network.

The Brittle Bone Disorders Consortium is part of the National Institutes of Health Rare Diseases Clinical Research Network. It is a multi-center program that focuses on understanding and providing better treatment options for all types of osteogenesis imperfecta (OI).

Consortium Spotlight: Advancing Discoveries in Brittle Bone Disorders:

The Brittle Bone Disorders Consortium (BBDC) brings together physicians, researchers, and educators to learn more about osteogenesis imperfecta (OI), a genetic disorder that mainly affects the development of the bones. The goal is to develop new and better treatments for patients with OI. Here, principal investigator Brendan Lee, MD, PhD, and Vernon Sutton, MD, share the history of the consortium, current research, and future plans.
Click here to read more.

Early-Stage Investigator Spotlight: Chaya Nautiyal Murali Gets Creative with Osteogenesis Imperfecta Research:

Chaya Nautiyal Murali, MD, is a pediatric geneticist at Baylor College of Medicine and a member of the Brittle Bone Disorders Consortium (BBDC). She is also an accomplished essayist, using her creative writing skills to highlight themes of identity, inheritance, and family through the lenses of immigration and genetics. Here, she shares her start in rare disease research, exciting discoveries, and future goals.
Click here to read more.

Patient Spotlight: Fynan Family Fueled by OI Research

Michelle Fynan, PhD, LMHC, is a mother of two daughters, age seven and four. She and her daughters are diagnosed with osteogenesis imperfecta (OI) type I, the mildest form of OI, which is characterized by bone fractures that often result from minor trauma. Here, Michelle shares her journey with OI, from adolescent struggles to finding her purpose as an OI activist and researcher.
Click here to read more.

Patient Advocate Spotlight: Tracy Hart Fosters Connections to Help Patients with Osteogenesis Imperfecta

Tracy Hart, chief executive officer of the Osteogenesis Imperfecta Foundation, serves as chair of the RDCRN’s Coalition of Patient Advocacy Groups.
Click here to read more.

Meet Dr. Francesca Tonelli, OIF Michael Geisman Fellow

By: Gabriela Beug, OIF Science and Media Communications Intern

As osteogenesis imperfecta is a rare bone disease, research grants remain difficult to acquire worldwide. The Osteogenesis Imperfecta Foundation makes research a priority through the Michael Geisman Fellowship program (created in memory of Michael Geisman, son of OI Foundation founder Gemma Geisman), which funds post-doctoral trainees whose research aims to predict, prevent, diagnose, and treat osteogenesis imperfecta (OI).

With the support of the Michael Geisman Fellowship program, awardees work to develop new approaches for therapies targeting OI. In the developmental stages, therapies are first tested on animal models (i.e. mice, zebrafish) before passing the requirements to move on to clinical trials. Studying diseases requires organisms with the same morphological and biochemical properties as well as a similar genome to humans. Both mice and zebrafish have a high level of genetic conservation – meaning a large part of their genome is identical to humans. While in zebrafish this number is around 70%, in mice it averages around 85%.  Mice and zebrafish offer an alternative to relying on human samples to test hypotheses, especially for rare bone disease where access to samples is limited.

The OI Foundation is proud to support Dr. Francesca Tonelli of University of Pavia in Pavia, Italy.

“I believe it is a unique experience to study a rare disease and I wish every scientist could have this opportunity at some point in their career. Even if I enjoy the individual aspects of lab work like creating animal models, the research in the OI field makes me feel like I will support other people and it is personally very rewarding. It’s the interaction with an individual with OI  and  the hope of finding a cure for them that make me passionate and persistent in testing new hypotheses until we can develop a cure.” – Dr. Francesca Tonelli

Francesca Tonelli obtained her bachelor’s degree in medical and pharmaceutical biotechnology from the University of Pavia in Pavia, Italy in 2012 and continued in the same field, completing her master’s degree in 2014. Her journey with osteogenesis imperfecta began by characterizing the dominant OI zebrafish model Chihuahua, which at the time was a new model for studying osteogenesis imperfecta. During her PhD she generated several new recessive OI zebrafish models by CRISPR Cas9 gene editing technique. In 2017, Tonelli received her Ph.D. in biomedical sciences under Dr. Antonella Forlino’s supervision. Continuing under her mentorship for her postdoctoral training, she is now applying her training to research in osteogenesis imperfecta. In her free time, Dr. Tonelli likes to read, kickbox, or scuba dive.

Areas of Expertise

• Crispr-Cas9 gene editing
• Designing, cloning, transcribing CRISPR constructs
• Generating zebrafish models to investigate skeletal diseases
• Drug screening: 4-PBA

It is well established that cellular stress is one of the main factors contributing to the osteogenesis imperfecta disease, which disrupts the homeostasis (the “well-being” of cells), leading to protein misfolding. The novel finding of Dr. Tonelli led to identifying chemical compounds such as 4-phenylbutyrate (4-PBA), a drug approved for urea cycle disorders whose beneficial chaperone activity also aids in ameliorating the bone phenotype of OI in the dominant and the recessive zebrafish model.

Her research now focuses on the study of bone formation, thanks to the zebrafish’s ability to regenerate the caudal fin. Caudal fin regeneration essentially mimics the dermal bone formation process similarly as it would occur during the human bone growth. Caudal fin regeneration can be exploited also to test the effect of new potential drugs.

Although 4-PBA has been identified as a potential therapeutic target, steps remain to transition from the lab to the translation in patients. Dr. Tonelli’s next step is to test a chemically modified version of 4-PBA, which would increase drug stability, specifically targeting bone tissue, making it more friendly for clinical trials in the future.

Selected Publications:

• Zebrafish: A Resourceful Vertebrate Model to Investigate Skeletal Disorders. Tonelli F, Bek JW, Besio R, De Clercq A, Leoni L, Salmon P, Coucke PJ, Willaert A, Forlino A. Front Endocrinol 2020 doi: 10.3389/fendo.2020.00489
• Novel RPL13 variants and variable clinical expressivity in a human ribosomopathy with spondyloepimetaphyseal dysplasia. Costantini A, Alm JJ, Tonelli F, Valta H, Huber C, Tran AN, Daponte V, Kirova N, Kwon YU, Bae JY, Chung WY, Tan S, Sznajer Y, Nishimura G, Näreoja T, Warren AJ, Cormier-Daire V, Kim OH, Forlino A, Cho TJ, Mäkitie O. J Bone Miner Res 2020 doi: 10.1002/jbmr.4177
• Crtap and p3h1 knock out zebrafish support defective collagen chaperoning as the cause of their osteogenesis imperfecta phenotype. Tonelli F, Cotti S, Leoni L, Besio R, Gioia R, Marchese L, Giorgetti S, Gistelinck C, Wagener R, Kobbe B, Larionova D, Fiedler I.A.K., Busse B, Eyre D, Rossi A, Witten PE, Forlino A. Matrix Biology 2020, (90): 40-60. doi: 10.1016/j.matbio.2020.03.004
• Bone biology: insights from osteogenesis imperfecta and related rare fragility syndromes.
  Besio R, Chow CW, Tonelli F, Marini JC, Forlino A. FEBS J. 2019, (15):3033-3056. doi: 10.1111/febs.14963.
• Steady-State and Pulse-Chase Analyses of Fibrillar Collagen. Forlino A, Tonelli F, Besio R. Methods Mol Biol. 2019;(1952):45-53. doi: 10.1007/978-1-4939-9133-4_4.
• Zebrafish Collagen Type I: Molecular and Biochemical Characterization of the Major Structural Protein in Bone and Skin.Gistelinck C, Gioia R, Gagliardi A, Tonelli F, Marchese L, Bianchi L, Landi C, Bini L, Huysseune A, Witten PE, Staes A, Gevaert K, De Rocker N, Menten B, Malfait F, Leikin S, Carra S, Tenni R, Rossi A, De Paepe A, Coucke P, Willaert A, Forlino A. Sci Rep. 2016, (6):21540.
• The chaperone activity of 4PBA ameliorates the skeletal phenotype of Chihuahua, a zebrafish model for dominant osteogenesis imperfecta. Gioia R.*, Tonelli F.*, Ceppi I., Biggiogera M., Leikin S., Fisher S., Tenedini E., Yorgan T.A., Schinke T., Tian K., Schwartz J.M., Forte F., Wagener R., Villani S., Rossi A. and Forlino A. Hum Mol Genet 2017, (26):2897-2911. * first co-authors