Department/College/UnitPhysical & Biological Sciences Division

TitleProfessor

AffiliationFaculty

Web SiteStone

Primary Office LocationPhysical Sciences Building
462

Additional Location(s)Physical Sciences Bldg 459 (Lab)

Mail StopChemistry

Biography, Education and Training

Dr. Michael D. Stone is a biochemist and professor at the University of California, Santa Cruz (UCSC), where his research focuses on ribonucleoproteins, particularly telomerase, a critical enzyme for maintaining chromosome stability. He earned his Bachelor’s degree in Biochemistry from the University of Pennsylvania and later completed his Ph.D. at UC Berkeley, followed by a postdoctoral fellowship at Harvard University. His research lab at UCSC uses single-molecule techniques to explore RNA and protein interactions, contributing to our understanding of telomere biology, RNA folding, and enzymatic processes relevant to aging and cancer​.

In response to the COVID-19 pandemic, Dr. Stone co-founded a diagnostic testing lab at UCSC, which significantly expanded testing capabilities in Santa Cruz County. This lab provided critical support to local healthcare systems by delivering reliable diagnostic services during the crisis​.

Alongside his research and public health efforts, Dr. Stone is passionate about teaching and mentoring undergraduates. He strives to create an engaging, supportive learning environment, integrating hands-on research with classroom instruction to help students develop critical thinking and a deeper appreciation for scientific inquiry.

Summary of Expertise

Molecular basis of telomere length and telomerase-related diseases; biophysical characterization of nucleic acids, structural basis for pre-mRNA splicing, RNA therapeutics for rare human disease

Research Interests

Single-molecule Biophysics and Enzymology; Structure, function, and assembly of the telomerase ribonucleoprotein, Fluorescence Resonance Energy Transfer (FRET), optical/magnetic trapping.

Telomeres are specialized chromatin structures that prevent deleterious chromosome fusion events by differentiating normal chromosome ends from sites of DNA damage. Telomere DNA is synthesized by the telomerase ribonucleoprotein (RNP), an enzyme comprised of the telomerase reverse transcriptase, telomerase RNA, and several additional protein cofactors. Telomerase activation is a tightly regulated process restricted to rapidly dividing cell types such as stem cells and the majority of human tumors. It is thus of direct medical importance to understand fundamental mechanisms governing telomerase assembly and function.

My laboratory takes a multi-disciplinary approach to study the structure and function of telomerase, combining established biochemical methods with emerging single molecule techniques which allow direct analysis of complex dynamics not possible with traditional ensemble measurements. For example, we employ single molecule fluorescence resonance energy transfer (smFRET) to monitor telomerase structure and dynamics during RNP assembly and catalysis. In addition, we utilize micro-manipulation techniques such as magnetic trapping to investigate the unique structural properties of telomere DNA and the molecular mechanisms of telomere remodeling proteins that contribute to telomerase regulation.

Students in my laboratory will have the opportunity to participate in diverse areas of research including: molecular biology, protein and nucleic acid biochemistry, design and fabrication of biophysical instrumentation, software development, and quantitative data analysis.

Selected Publications

• Real-time detection of human telomerase DNA synthesis by multiplexed single-molecule FRET. Hentschel J, Badstübner M, Choi J, Bagshaw CR, Lapointe CP, Wang J, Jansson LI, Puglisi JD, Stone MD. Biophys J. 2023 Sep 5;122(17):3447-3457. doi: 10.1016/j.bpj.2023.07.019. Epub 2023 Jul 27.

• An intronic RNA element modulates Factor VIII exon-16 splicing. Victor Tse, Guillermo Chacaltana, Martin Gutierrez, Nicholas M. Forino, Arcelia G. Jimenez, Hanzhang Tao, Phong H. Do, Catherine Oh, Priyanka Chary, Isabel Quesada, Antonia Hamrick, Sophie Lee, Michael D. Stone, Jeremy R. Sanford Nucleic Acids Res. 2023 Nov 14.

• A method for campus-wide SARS-CoV-2 surveillance at a large public university. Terren Chang , Jolene M Draper , Anouk Van den Bout , Ellen Kephart, Hannah Maul-Newby, Yvonne Vasquez, Jason Woodbury , Savanna Randi, Martina Pedersen, Maeve Nave, Scott La, Natalie Gallagher, Molly M McCabe, Namrita Dhillon, Isabel Bjork, Michael Luttrell, Frank Dang, John B MacMillan, Ralph Green, Elizabeth Miller, Auston M Kilpatrick, Olena Vaske, Michael D Stone, Jeremy R Sanford. PLoS ONE 2021 Dec 17;16 (12)

• Folding heterogeneity in the essential human telomerase RNA three-way junction. Christina Palka, Nicholas Forino, Jendrik Hentschel, Rhiju Das, and Michael D. Stone. RNA. Dec. 26, 2020 (12):1787-1800.

• Telomere DNA G-quadruplex folding within actively extending human telomerase. Linnea I. Jansson, Jendrik Hentschel, Joseph W. Parks, Terren R. Chang, Cheng Lu, Rishika Baral, Clive R. Bagshaw, and Michael D. Stone. PNAS May 7, 2019 116 (19) 9350-9359.

• Stepwise protein-mediated RNA folding directs assembly of telomerase ribonucleoprotein. Stone, M.D., Mihalusova, M., O'Connor C, M., Prathapam, R., Collins, K., and Zhuang, X. (2007). Nature 446, 458-461