My research focuses on understanding the mechanisms establishing and regulating epigenetic information, and how epigenetic systems ultimately contribute to gene regulation, disease, and other phenotypes. In addition to the genetic information encoded within the DNA, other forms of information exist in the cell. Epigenetic information is heritable, affects gene expression states and phenotypes, but is independent of DNA sequence. Examples of epigenetic systems include DNA methylation, histone modifications, and chromatin structure. These epigenetic systems play vital roles in gene regulation, and defects in epigenetic regulation have been implicated in a variety of human diseases including cancer. My lab uses the fruit fly Drosophila melanogaster as a model system to investigate epigenetic systems and their influence on development and gene regulation. Currently, there are three on-going projects in the lab:

• The HP1 protein family: Heterochromatin protein 1a (HP1a) was discovered as the first heterochromatin-associated protein. Its binding characterizes the heterochromatic regions of the fly genome, and homologs have been identified in species ranging from yeast to humans. The HP1a protein contains two conserved domains, the chromo domain, and the chromo-shadow domain. Based on this domain structure, four additional HP1 family proteins have been identified in Drosophila melanogaster. Of these, HP1B and HP1C, like HP1a, are ubiquitously expressed, while HP1D/RHINO and HP1E are restricted to the germline in females and males respectively. While HP1a binds large domains in heterochromatin, it also shows binding to active transcription start sites, where it is generally found in the company of HP1B and/or HP1C. We are using molecular genetics and genomics approaches to understand the relationship between HP1a, HP1B, and HP1C, and their effect on gene regulation.
• The role of epigenetics in exercise response: Exercise is a common form of treatment recommended to combat the increasing obesity problem observed in many countries. How individuals respond to exercise is highly variable, and the source of this variation is not well understood. We are using the fruit fly Drosophila melanogaster as a model for exercise biology. Taking advantage of the genetics resources available in Drosophila, our experiments are designed to determine the relative importance of genetics and epigenetics in generating the variability in exercise response.
• Epigenetic contributions to sex differences in aging: Typically, with age, both genome and epigenome stability decreases. DNA repair pathways function less well, chromatin modifiers become misregulated, and noise in gene expression increases. Currently, it is not clear if these same processes contribute to the sex differences in aging seen in many species. Together with our colleges in IISAGE, we investigate this question using Drosophila as a model. We are manipulating genome content, heterochromatin amount, DNA repair pathways, and more to define their role in sex-specific aging.

• Seminar in Genetics
• Investigative Techniques
• CLOne – Chromatin Laboratory 1
• Genetics
• Epigenetics
• Epigenetics Discussion/Journal Club

Trainees

• Jalen Bynum
• Heidi M. G. Johnson
• Sarah Sims
• James C. Walts
• Tristan Young

Alumni

• Bre’ Minniefield, postdoctoral fellow
• Amit Paul, postdoctoral fellow
• John M. Schoelz, PhD
• Louis Watanabe, PhD
• Justina X. Feng, MS
• Jordan Favors, MS
• Samuel Gregory, MS
• Mina Momeni, MS
• Benjamin B. Mills, MS
• Christine McBride, MS

For a full list of publications, please visit Dr. Riddle's PubMed entry.

• Adler FR, Anderson ARA, Bhushan A, Bogdan P, Bravo-Cordero JJ, Brock A, Chen Y, Cukierman E, DelGiorno KE, Denis GV, Ferrall-Fairbanks MC, Gartner ZJ, Germain RN, Gordon DM, Hunter G, Jolly MK, Karacosta LG, Mythreye K, Katira P, Kulkarni RP, Kutys ML, Lander AD, Laughney AM, Levine H, Lou E, Lowenstein PR, Masters KS, Pe'er D, Peyton SR, Platt MO, Purvis JE, Quon G, Richer JK, Riddle NC, Rodriguez A, Snyder JC, Szeto GL, Tomlin CJ, Yanai I, Zervantonakis IK, and Dueck HR. Modeling collective cell behavior in cancer: perspectives from an interdisciplinary conversation. Cell Syst 14(4):252-257, doi:10.1016/j.cels.2023.03.002.
• Schoelz JM and Riddle NC. Functions of HP1 proteins in transcriptional regulation (2022) Epigenetics & Chromatin 15, 14, https://doi.org/10.1186/s13072-022-00453-8.
• Bronikowski AM, Meisel RP, Biga PR, Walters JR, Mank JE, Larschan E, Wilkinson GS, Valenzuela N, Conard AM, de Magalhães JP, Duan J(E), Elias AE, Gamble T, Graze RM, Gribble KE, Kreiling JA, and Riddle NC. Sex-specific aging in animals: Perspective and future directions (2022) Aging Cell 21, e13542, https://doi.org/10.1111/acel.13542.
• Watanabe LP and Riddle NC. Exercise-induced changes in climbing performance (2021) R Soc Open Sci 8: 211275, https://doi.org/10.1098/rsos.211275.
• Schoelz JM, Feng JX, and Riddle NC. The Drosophila HP1 family is associated with active gene expression across chromatin contexts (2021) Genetics 219(1):iyab090.
• Brodie B, Gregory B, Lisch D, and Riddle NC. The epigenome and beyond: How does non-genetic inheritance change our view of evolution? (2021) Integr Comp Bio.
• Watanabe LP and Riddle NC. GWAS reveal a role for the central nervous system in regulating weight and weight change in response to exercise (2021) Sci Rep 11(1):5144.
• Riddle NC. Variation in the response to exercise stimulation in Drosophila: Marathon runner versus sprinter genotypes (2020) J Exp Bio 223(Pt 18):jeb229997.
• Feng, JX and Riddle NC. Epigenetics and genome stability (2020) Mammalian Genome Apr 15. doi: 10.1007/s00335-020-09836-2.
• Watanabe LP, Gordon C, Momeni MY, and Riddle NC. Genetic networks underlying natural variation in basal and induced activity levels in Drosophila melanogaster (2020) G310(4):1247-1260.
• Riddle NC. Drosophila melanogaster, a new model for exercise research (2019) Acta Physiologica (Oxf) Jul 25:e13352. Invited editorial.

• Named New Investigator for the UAB Nutrition Obesity Research Center (NORC), 2015
• Provost's Award for Faculty Excellence in Academic Engagement and Global Citizenship, 2014
• American Association for the Advancement of Science
• The Genetics Society of America
• UAB Sigma Xi – President-Elect (2017-2018); President (2018-2019)
• 2016 The John R Durant Award for Excellence in Cancer Research, 1st Place, Junior Faculty Category at the UAB Comprehensive Cancer Center 18th Annual Research Retreat and Research Competition
• 2013 The John R Durant Award for Excellence in Cancer Research, 2nd Place, Junior Faculty Category at the UAB Comprehensive Cancer Center 16th Annual Research Retreat and Research Competition

• UAB Genetics Club