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TSC Biosample Repository & Natural History Database

Get Involved

The TSC Natural History Database captures clinical data provided by physicians to document the impact of the disease on a person’s health over his or her lifetime. The TSC Biosample Repository stores samples of blood, DNA, and tissues scientists can use in their research. The samples we collect are all linked to clinical data in the TSC Natural History Database.

More than 2,600 people with TSC are enrolled in the Natural History database and more than 1,000 people have contributed biosamples. The biosamples and data about individuals who provided samples help researchers discover biomarkers of TSC, test potential drug treatments, and determine why TSC is so different from person to person. If you are interested in participating or learning more, please fill out the interest form at the bottom of the page.

Testimonials

Biosample contribution

Blood samples

The TSC Biosample Repository is collecting samples from TSC Natural History Database participants at specific clinics and via mobile blood collections. In coordination with a national mobile phlebotomy service (TravaLab or ExamOne), the TSC Alliance can collect blood samples from anyone in the United States with TSC. If you are interested in participating or learning more, please fill out the brief interest form at the bottom of the page. Someone from the Science and Medical team will be in touch shortly. You can also let us know your interest by emailing biosample@tscalliance.org. The TSC Alliance hopes to collect blood samples from participants once per year.

The TSC Alliance also accepts blood samples from volunteers enrolled in the TSC Natural History Database at the following sites:

Circle icons indicate a database only site meaning that biosamples are not collected on site. Pushpins indicate sites approved to collect biosamples on site

List of current sites

  1. Boston Children’s Hospital, Boston, MA (Mustafa Sahin, MD, PhD)
  2. Children’s Hospital Colorado, Aurora, CO (Susan Koh, MD) [database only]
  3. Children’s National Medical Center, Washington, DC (William McClintock, MD)
  4. Cincinnati Children’s Hospital Medical Center, Cincinnati, OH (Darcy A. Krueger, MD, PhD)
  5. Cleveland Clinic, Cleveland, OH (Ajay Gupta, MD)
  6. Le Bonheur Children’s Hospital, Memphis, TN (Jim Wheless, MD)
  7. Loma Linda University Medical Center, Loma Linda, CA (Stephen Ashwal, MD) [database only]
  8. Massachusetts General Hospital, Boston, MA (Elizabeth A. Thiele, MD, PhD)
  9. Minnesota Epilepsy Group, PA, Roseville, MN (Doug Smith, MD)
  10. New York University Langone Medical Center, New York, NY (Josiane LaJoie, MD)
  11. Nicklaus Children’s Hospital, Miami, FL (Paula Schleifer, MD)
  12. Texas Children’s Hospital Baylor College of Medicine, Houston, TX (Howard L. Weiner, MD)
  13. Texas Scottish Rite Hospital for Children, Dallas, TX (Steven P Sparagana, MD)
  14. Université de Montréal Sainte-Justine, Montreal, Canada (Philippe Major, MD)
  15. Université de Montréal, Montreal, Canada (Mark Keezer, BA, BSc, MSc, MDCM, PhD)
  16. University of Alabama, Birmingham, AL (Martina Bebin, MD, MPA)
  17. University of California Los Angeles (UCLA), Los Angeles, CA (Rajsekar Rajaraman, MD)
  18. University of Chicago, Chicago, IL (James Tonsgard, MD) [database only]
  19. University of Iowa, Iowa City, IA (Michael Ciliberto, MD)
  20. University of Pennsylvania, Philadelphia, PA (Katherine Nathanson, MD) [database only]
  21. University of Texas Health Science Center, Houston, TX (Hope Northrup, MD)
  22. Washington University, St. Louis, MO (Michael Wong, MD, PhD)
  23. TSC Alliance, Silver Spring, MD (remote consenting and mobile sample collections)

Individuals with TSC seen at one of the participating institutions may ask their health care provider or clinic coordinator about participating in the TSC Natural History Database and Biosample Repository. If you are interested in participating or learning more, please fill out the brief interest form at the bottom of the page.

Research updates

Biosample distribution

 

Since inception, the TSC Biosample Repository has distributed 2,237 samples to 47 distinct researchers for 56 distinct projects. Some examples of projects conducted using biosamples include bioassays measuring levels of cellular activity, screening for novel therapeutic targets, detecting biomarkers, and measuring metabolites in blood and comparing them with phenotypes reported in the TSC Natural History Database. DNA extracted from cheek swabs and blood samples can be used for genetic testing to detect TSC variants, and plasma from blood samples can be used to assay for predictive biomarkers or biomarkers of response and tissue samples are used to detect tissue-specific markers and cell types that are important for studying TSC progression.

Publications using TSC biosamples

  • Hsieh L, Wen J, Nguyen L, Zhang L, Getz S, Torres-Reveron J, Wang Y, Spencer D, and Bordey A. Ectopic HCN4 expression drives mTOR-dependent epilepsy in mice. Sci Transl Med. 2020 Nov 18;12(570):eabc1492. doi: 10.1126/scitranslmed.abc1492. Read the Article.
    • The authors found a link between the expression of a channel protein called HCN4 (hyperpolarization-activated cyclic-gated potassium channel isoform 4) and seizure activity when present in neurons in mouse brains. They found that elevated mTOR activity led to HCN4 expression in mice and found HCN4 expression in brain tissues resected from patients with TSC.
  • Salles DC, Asrani K, Woo J, Vidotto T, Liu HB, Vidal I, Matoso A, Netto GJ, Argani P, Lotan TL. GPNMB expression identifies TSC1/2/mTOR-associated and MiT family translocation-driven renal neoplasms.J Pathol. 2022 Jun;257(2):158-171. doi: 10.1002/path.5875. Epub 2022 Mar 29. PMID: 35072947; PMCID: PMC9310781. Read the article.
    • The authors found that GPNMB (glycoprotein nonmetastatic B) was upregulated following TSC2loss in a MiT/TFE‐ and mTORC1‐dependent fashion in cell lines. Additionally, renal tumors in Tsc2 +/− A/J mice showed upregulation of GPNMB compared with normal kidney. Mean GPNMB expression was comparable between translocation renal cell carcinomas and other TSC1/2/MTOR alteration‐associated renal tumors (including ESC, LOT, AML, and PEComa).
  • Asrani, K., Woo, J., Mendes, A.A. et al. An mTORC1-mediated negative feedback loop constrains amino acid-induced FLCN-Rag activation in renal cells with TSC2 loss. Nat Commun 13, 6808 (2022). Read the article.
    • The authors utilized the human embryonic kidney HEK293T cells with or without somatic genomic deletion of TSC1, TSC2 or TSC1/2via CRISPR-Cas9 genome editing from the Biosample Repository to show data indicating the existence of a negative feedback loop that constrains amino acid-induced, FLCN:FNIP2-mediated RagC activity in renal cells with constitutive mTORC1 signaling, and the resulting MiT/TFE hyperactivation may drive oncogenesis with loss of the TSC2 tumor suppressor.
  • Rubtsova V, Chun Y, Kim J, Ramirez CB, Jung S, Choi W, Kelly ME, Lopez ML, Cassidy E, Rushing G, Aguiar DJ, Ling Lau W, Ahdoot RS, Smith M, Edinger AL, Lee S, Jang C, and Lee G. Circulating biomarkers of kidney angiomyolipoma and cysts in tuberous sclerosis complex patients. iScience, 2024 Jun. doi: 10.1016/j.isci.2024.110265. Read the article.
    • The study conducted metabolomics and utilized on plasma from kidney angiomyolipoma/cyst-positive or -negative TSC patients to identify potential diagnostic markers of kidney angiomyolipoma’s (AML) in tuberous sclerosis complex. The authors identified seven chemical markers in AML/cyst-positive samples that could point to identifying kidney/metabolic disease in TSC. These seven markers even remained significant when compared to healthy control samples.

For researchers

If you are a researcher interested in using samples from the TSC Biosample Repository in your work, please see here for more information.

Post-mortem brain donation

The University of Maryland Brain and Tissue Bank (MBTB) makes arrangements for this type of precious gift on behalf of the TSC Alliance. Individuals living anywhere in the United States who wish to donate whole brain tissue after death should contact MBTB at btbumab@som.umaryland.edu. If death is imminent and you would like to donate brain tissue, please call the MBTB as soon as possible at 1-800-847-1539.

Successful donation rests on swift and thorough communication between family members, healthcare professionals, and the MBTB. Although the MBTB will make every effort to retrieve tissue in an emergency, tissue recovery may be impossible if there is no advance notice.  Please click here for instructions on how to register in advance for postmortem donation. There is no cost to the family to donate.

Steven Sparagana Legacy Fund

The TSC Natural History Database and Biosample Repository are funded by donors who contribute to funds such as the Steven Sparagana Legacy Fund, which provides an ongoing source of revenue in support of the Natural History Database and Biosample Repository as a tribute to Dr. Sparagana’s contributions to the creation and ongoing success of these invaluable tools. Learn more about the fund and donate here.

Acknowledgments

The TSC Natural History Database and Biosample Repository are governed and wholly funded by the TSC Alliance thanks to generous support from Lorne Waxlax, William Watts, Dr. Michael and Janie Frost, Janice and Julian Gangolli Family Fund, Jim and the late Andrea Maginn, and many additional donors through the Unlock the Cure campaign.

Our thanks to UCB, Inc. for supporting translation of consent forms for this project into Spanish.

Interested in participating in the TSC Natural History Database and Biosample Repository Project?

Fill out the brief interest form below and a TSC Alliance Science and Medical team member will be in touch with you shortly.

Biosample Repository Project Interest Form
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