About

Norbert O. Reich is a Distinguished Professor in the Department of Chemistry & Biochemistry at the University of California, Santa Barbara. His specialization includes Materials Chemistry, Biochemistry & Biophysics, Biomedical Sciences, Biology-Inspired Chemistry & Physics, Devices, Assembly & Nanochemistry, Structural Chemistry, Spectroscopy & Advanced Analysis. He received his Ph.D. from the University of California, San Francisco in 1984 and completed an NIH post-doctoral fellowship at UCSF before joining UCSB in 1987. His research focuses on the study of enzyme function, particularly catalytic and specificity mechanisms, with the long-term goal of developing enzyme inhibitors with potential therapeutic applications. His work involves bacterial and mammalian enzymes involved in DNA methylation and telomerase, aiming to understand their mechanisms and develop novel therapeutics. Reich's research also includes developing new methods and technologies to investigate cell-biological, biochemical, and biomedical questions, such as fluorescence-based protein-DNA interaction assays, nanoshell technology for targeted drug delivery, and gene silencing techniques. His contributions have advanced understanding of DNA methyltransferases, enzyme mechanisms, and the development of inhibitors relevant to cancer and infectious diseases.

Research topics

• Chemistry
• Biology
• Biochemistry
• Nanotechnology
• Political science

Selected publications

• Mechanism of non-coding RNA regulation of DNMT3A

  Epigenetics & Chromatin · 2025-03-28

  articleOpen accessSenior author

  BACKGROUND: De novo DNA methylation by DNMT3A is a fundamental epigenetic modification for transcriptional regulation. Histone tails and regulatory proteins regulate DNMT3A, and the crosstalk between these epigenetic mechanisms ensures appropriate DNA methylation patterning. Based on findings showing that Fos ecRNA inhibits DNMT3A activity in neurons, we sought to characterize the contribution of this regulatory RNA in the modulation of DNMT3A in the presence of regulatory proteins and histone tails. RESULTS: We show that Fos ecRNA and mRNA strongly correlate in primary cortical neurons on a single cell level and provide evidence that Fos ecRNA modulation of DNMT3A at these actively transcribed sites occurs in a sequence-independent manner. Further characterization of the Fos ecRNA-DNMT3A interaction showed that Fos-1 ecRNA binds the DNMT3A tetramer interface and clinically relevant DNMT3A substitutions that disrupt the inhibition of DNMT3A activity by Fos-1 ecRNA are restored by the formation of heterotetramers with DNMT3L. Lastly, using DNMT3L and Fos ecRNA in the presence of synthetic histone H3 tails or reconstituted polynucleosomes, we found that regulatory RNAs play dominant roles in the modulation of DNMT3A activity. CONCLUSION: Our results are consistent with a model for RNA regulation of DNMT3A that involves localized production of short RNAs binding to a nonspecific site on the protein, rather than formation of localized RNA/DNA structures. We propose that regulatory RNAs play a dominant role in the regulation of DNMT3A catalytic activity at sites with increased production of regulatory RNAs.

  PublisherOA PDFDOI

• Abstract 1663 Bringing CRISPR-Based Inquiry into the High School

  Journal of Biological Chemistry · 2025-05-01

  articleOpen accessSenior author

  SciTrek is an outreach program from the University of California at Santa Barbara that engages K-12 students in authentic inquiry guided by university students. Scitrek has since worked closely with the Santa Barbara School District (59.9% Latino, 31.1% White, 2.9% Asian, 0.7% Black, 4.9% Multiracial, 0.2% Native, 31.5% economically disadvantaged (US News)) and private schools to bring engaging science modules to local students of all socioeconomic backgrounds. Prior results of the SciTrek program have demonstrated significant improvement in the three metrics of 1) students' content understanding, 2) critical thinking, and 3) attitudes toward science.

  PublisherOA PDFDOI

• Allosteric Inhibitors of Cell-Cycle-Regulated Methyltransferase for Novel Antibiotic Development

  ACS Omega · 2025-04-09

  articleOpen accessSenior authorCorresponding

  Cell-cycle-regulated methyltransferase (CcrM) plays a crucial role in regulating important cellular processes that are essential for proper cell division and growth; disruptions of these processes can attenuate the bacteria's viability. Notably, CcrM homologs are present across a set of diverse human pathogens, suggesting that selective inhibition of CcrM over human DNA methyltransferases (DNMT's) could offer a new strategy for combating human bacterial pathogens, leading to the development of novel antibiotics. Herein, we report the screening of two open-access chemical libraries-the National Cancer Institute Developmental Therapeutic Program Diversity Set VII and Medicines for Malaria Venture Global Health Priority Box-and identified four structurally diverse inhibitors of CcrM. Among these, two inhibitors displayed both micromolar affinity and high selectivity for CcrM over human DNA methyltransferase 3A, highlighting their potential as leads for a new class of antibiotics.

  PublisherDOI

• Abstract 2457 SciTrek: High school inquiry module on electrochemistry and glucose detection

  Journal of Biological Chemistry · 2025-05-01

  articleOpen accessSenior author

  We have developed a glucose sensing authentic inquiry module for high school students using an electrochemical sensor and glucose oxidase to detect glucose. This 5-day module focuses on equipping students with critical thinking and data analysis skills, while demonstrating the real-world applications of electrochemistry, biochemistry, and medicine. Each day of the module highlights how these fields collaboratively address complex, real-world problems. Beyond scientific skills, the program emphasizes cultivating practical abilities in scientific inquiry and research methodology, as well as heightening their interest in science through helping students grasp the importance of science subjects via their real-world applications.

  PublisherOA PDFDOI

• Structural Investigations of Phthalazinone Derivatives as Allosteric Inhibitors of Human DNA Methyltransferase 3A

  ACS Medicinal Chemistry Letters · 2024-04-08 · 3 citations

  articleOpen accessSenior authorCorresponding

  The development of new therapeutics targeting enzymes involved in epigenetic pathways such as histone modification and DNA methylation has received a lot of attention, particularly for targeting diverse cancers. Unfortunately, irreversible nucleoside inhibitors (azacytidine and decitabine) have proven highly cytotoxic, and competitive inhibitors are also problematic. This work describes synthetic and structural investigations of a new class of allosteric DNA methyltransferase 3A (DNMT3A) inhibitors, leading to the identification of several critical pharmacophores in the lead structure. Specifically, we find that the tetrazole and phthalazinone moieties are indispensable for the inhibitory activity of DNMT3A and elucidate other modifiable regions in the lead compound.

  PublisherOA PDFDOI

• Improving 7th grade students’ understanding of how science works

  Research Square · 2024-09-25

  preprintOpen access1st authorCorresponding
  PublisherOA PDFDOI

• Mechanism of non-coding RNA regulation of DNMT3A and its relation to histones, regulatory proteins, and clinically relevant mutations

  Research Square · 2024-10-07

  preprintOpen accessSenior author
  PublisherOA PDFDOI

• High fidelity DNA strand-separation is the major specificity determinant in DNA methyltransferase CcrM’s catalytic mechanism

  Nucleic Acids Research · 2023-06-16 · 5 citations

  articleOpen accessSenior author

  Strand-separation is emerging as a novel DNA recognition mechanism but the underlying mechanisms and quantitative contribution of strand-separation to fidelity remain obscure. The bacterial DNA adenine methyltransferase, CcrM, recognizes 5'GANTC'3 sequences through a DNA strand-separation mechanism with unusually high selectivity. To explore this novel recognition mechanism, we incorporated Pyrrolo-dC into cognate and noncognate DNA to monitor the kinetics of strand-separation and used tryptophan fluorescence to follow protein conformational changes. Both signals are biphasic and global fitting showed that the faster phase of DNA strand-separation was coincident with the protein conformational transition. Non-cognate sequences did not display strand-separation and methylation was reduced > 300-fold, providing evidence that strand-separation is a major determinant of selectivity. Analysis of an R350A mutant showed that the enzyme conformational step can occur without strand-separation, so the two events are uncoupled. A stabilizing role for the methyl-donor (SAM) is proposed; the cofactor interacts with a critical loop which is inserted between the DNA strands, thereby stabilizing the strand-separated conformation. The results presented here are broadly applicable to the study of other N6-adenine methyltransferases that contain the structural features implicated in strand-separation, which are found widely dispersed across many bacterial phyla, including human and animal pathogens, and some Eukaryotes.

  PublisherOA PDFDOI

• Ochrona konsumenta przed ograniczeniami wolnej konkurencji na rynku towarów konsumpcyjnych w RFN

  Studia Prawnicze / The Legal Studies · 2023-04-30

  articleOpen access1st authorCorresponding
  PublisherDOI

• In silico study of selective inhibition mechanism of S-adenosyl-L-methionine analogs for human DNA methyltransferase 3A

  Computational Biology and Chemistry · 2022-11-28 · 5 citations

  articleSenior authorCorresponding
  PublisherDOI

Recent grants

• NIH Grant R01GM056289

  NIH · $566k · 2002

• Mechanistic investigation of processive and distributive DNA modification

  NSF · $609k · 2018–2024

• NIH Grant R01GM061821

  NIH · $286k · 2004

• NIH Grant R01GM046333

  NIH · $520k · 1996

• NIH Grant R43AI048377

  NIH · $121k · 2001

Frequent coauthors

• Gary B. Braun

  66 shared

• Martin Moskovits

  University of California, Santa Barbara

  27 shared

• R. August Estabrook

  University of California, Santa Barbara

  26 shared

• Demosthenes Morales

  Los Alamos National Laboratory

  21 shared

• P.R. Ortiz de Montellano

  Center for Research and Advanced Studies of the National Polytechnic Institute

  20 shared

• Ted A. Laurence

  Lawrence Livermore National Laboratory

  17 shared

• Stephanie Wilkinson

  University of California, Santa Barbara

  16 shared

• Geoffrey F. Strouse

  Florida State University

  15 shared

Awards & honors

• Regent's Junior Faculty Fellowship (1987)
• American Cancer Society Faculty Research Award (1991)
• UC President's Award for Excellence in Undergraduate Researc…