Melanie McReynolds

About Me

Dr. Melanie R. McReynolds is a HHMI Hanna H. Gray Fellow and Rising Assistant Professor at the Pennsylvania State University, where her research focuses on the intersection of metabolic decline and aging. Melanie holds a B.S. degree in Chemistry and Physics from Alcorn State University. She participated in the NIH funded Alcorn State to Penn State Bridges to the Doctorate Program where she obtained her M.S. degree in Biological Sciences. Dr. McReynolds completed her Ph.D. in Biochemistry, Microbiology and Molecular Biology at the Pennsylvania State University. Melanie was recognized as a Rising Star on the CellPress list of Top 100 Inspiring Black Scientists in America during her postdoctoral tenure at Princeton University and aims to inspire the next generation of scientists to trust that all things will work together for those who believe. Melanie a biochemist specializing in understanding the connection between metabolic stress and aging. She has over a decade of research, mentoring, and teaching experience that she is excited to offer back to the Penn State Community. Melanie is on the trajectory to establish her independent research group, where her lab will shed light on metabolic aging and disease. She is returning to Penn State as the Dorothy Foehr Huck and J. Lloyd Huck Early Career Chair in Biochemistry and Molecular Biology—effective January 2022.

Program or Departmental Affiliations

• The BMMB Graduate Program
  
   
• The Molecular, Cellular, and Integrative Biosciences Program

Editorial Boards & Professional Organizations

• Liaison, HHMI Hanna H. Gray Fellows Program

• Editorial Board Member, Physiological Genomics

Research Summary

Aging is the strongest risk factor for the most prevalent diseases in developed nations, including cancer, diabetes, cardiovascular, and neurodegenerative disorders. Demographics are projected to continue to shift toward aged individuals within our population. Therefore, to identify mechanisms that will promote healthier aging in the 21^st century, my research program aims to explore the intersection between metabolic decline and aging. I hope to discover how NAD⁺ homeostasis is achieved, and more generally how metabolism responds to stress-induced perturbations. By improving our understanding of the in vivo metabolic fluxes that occur in stress-induced aged models, we expect to uncover targetable molecular mechanisms that will enable the development of therapeutics and nutraceuticals to restore youthful metabolism.

I am broadly interested in understanding the biochemistry behind aging, and its intersection with stress, with the long-term goal of identifying strategies that promote healthier aging. Characterizing metabolic adaptation to acute and chronic stress in aged-related disease models will help illuminate age-related metabolic defects and reveal metabolic homeostasis mechanisms (Figure 1). As a scientist working at the interface of chemistry and biology, my research program will take advantage of high-resolution liquid-chromatography mass spectrometry (HR-LCMS) coupled to in vivo isotope tracing to: 1) elucidate how NAD⁺ homeostasis is achieved and fails over the lifespan, 2) uncover how toxic circulating small molecules contribute to aging and aged-related disorders, and 3) reveal stress-induced metabolic alterations in aging and aged-related disorders.

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Overall Strengths and Feasibility:

My research directions draw and build on my experience with isotope tracing and quantitative mass spectrometry, NAD⁺ metabolism, model organisms, and biochemical analyses. They will 1) answer the fundamental questions at the intersection of metabolic decline and aging, 2) attract external funding in addition to my HHMI Hanna H. Gray award and 3) afford exciting research and training opportunity for future mentees—at the postdoctoral, graduate and undergraduate stage. Better understanding of the in vivo metabolic fluxes in stress-induced aged models will provide the scientific underpinnings for the development of effective therapeutics and nutraceuticals for restoring youthful metabolism.

Honors and Awards

• Inaugural Intersections Science Fellow, 2021
  
   
• University of Utah Rising Stars in Metabolism, 2021
  
   
• HHMI Hanna H. Gray Fellows Program; 2018
  
   
• Burroughs Wellcome Fund Postdoctoral Research Enrichment Program; 2018
  
   
• Ruth L. Kirschstein National Research Service Award (F32) – Declined; 2018
  
   
• University Student Way Paver Award—Council College of Multicultural Leaders (CCML), Penn State University; 2017
  
   
• FASEB MARC Travel Award- Postdoctoral Preparation Institute Workshop; 2016
  
   
• ASBMB 2016 Best Thematic Poster Award- Metabolism, Disease and Drug Design; 2016
  
   
• St. Jude National Graduate Student Symposium (NGSS)—Invited/Selected Participant; 2016
  
   
• ASBMB MAC Travel Award- Experimental Biology meeting; 2016
  
   
• FASEB MARC Travel Award- FASEB Grant Writing Seminar & Responsible Conduct of Research Workshop; 2015
  
   
• FASEB MARC Program Poster/Oral Presentation Travel Award- GSA: 20^th International C. elegans meeting; 2015
  
   
• Alfred P. Sloan MPHD Scholar, Penn State University; 2014
  
   
• Bunton-Waller Fellowship, Penn State University; 2012

Selected Publications (McReynolds on Google Scholar)

Peer Reviewed:

• Lengefeld, J., Cheng, C.W., Maretich, P., Blair, M., Hagen, H., McReynolds, M.R., Sullivan, E., Mayors, K., Roberts, C., Kang, J.K., Steiner, J., Miettinen, T.P., Manalis, S.R., Antebi, A., Rabinowitz, J.D., Morrison, S., Lees, J.A., Boyer, L., Yilmaz, O., and A. Amon. Cell size is a determinant of stem cell potential during aging. (2021). Science Adavnces. https://doi.org/10.1101/2020.10.27.355388
  
   
• Chen, L., Lu, W., Wang, L., Xing, X., Zeng, X., Muscarekka, A.D., Shen, Y., Cowan, A., McReynolds, M.R., Kennedy, B., Lato, A.M., Campagna, S.R., Singh, M., and J.D. Rabinowtiz. (2021). Metabolite discovery through global annotation of untargeted metabolomics data. Nature Methods. https://doi.org/10.1038/s41592-021-01303-3
  
   
• McReynolds, M.R.*, Chellappa, K., C.*, Chiles, E., Jankowski, Shen, Y., Chen, L., Descamps, H., Mukherjee, S., Bhay, Y.R., Chu, Q., Ji, X., Song, F., Botolin, P., Lu, W., Thaiss, C., Su, X., Long, F., Rabinowitz, J.D. and J.A. Baur. (2021). NAD⁺ flux is maintained in aged mice despite lower concentrations. Cell Systems. https://doi.org/10.1016/j.cels.2021.09.001
  
   
• Schild, T., McReynolds, M.R., Shea, C., Low, V., Asara, J., Dephoure, N., Rabinowitz, J.D., Gomes, A.P. and J. Blenis. (2021). NADK is activated by oncogenic KRAS signaling to sustain pancreatic ductal adenocarcinoma. Cell Reports. https://doi.org/10.1016/j.celrep.2021.109238

• Minhas, P., Hernandez, A.L.*, McReynolds, M.R.*, He, J., Joshi, A., Linde, M., Wilson, E.N., Rubin, A.J., Wang, Q.A., Swarovski, M., Majeti, R., Mochly-Rosen, D.R., Weissman, I., Longo, F.M., Rabinowitz, J.D. and K.I. Andreasson. (2020). Restoring metabolism oof myeloid cells reverses cognitive decline in ageing. Nature. https://doi.org/10.1038/s41586-020-03160-0
  
   
• Luonogo, T.S., Eller, J.M., Lu, M.J., Niere, M., Raith, F., Perry, C., Bornstein, M.R., Oliphint, P., Wang, L., McReynolds, M.R., Migaud, M.E., Rabinowitz, J.D., Johnson, F.B., Johnsson, K., Ziegler, M., Cambronne, X.A., and J.A. Baur. (2020). SLC25A51 is a mammalian mitochondrial NAD transporter. Nature. https://doi.org/10.1038/s41586-020-2741-7
  
   
• Chini, C.S., Tarrago, M.G., Warner, G.M., de Oliveira, G.C., Espindola-Netto, J.M., Puranik, A.S., Kashyap, S., Peclat, T.R., Dang, K., Clarke, S., Childs, B.G., Hogan, K.A., Kanamori, K.S., Witte, M.A., Vidal, P., Chellappa, K., McReynolds, M.R., Jankowski, C., Tchkonia, T., Kirkland, J.L., van Deursen, J.M., Baker, D.J., Cohen, R., van Schooten, W., Rabinowitz, J.D., Baur, J.A and E.N. Chini. (2020). Expression of the ecto-enzymes CD38 is induced by senescent cells and decreases tissues NAD⁺ during aging by depleting its precursor NMN. Nature Metabolism. https://doi.org/10.1038/s42255-020-00298-z

• Lu, W., Xing, X., Wang, L., Chen, L., Zhang, S., McReynolds, M.R. and J.D. Rabinowitz. (2020). Improved annotation of untargeted metabolomics data through buffer modifications that shift adduct mass and intensity. Analytical Chemistry. DOI: 10.1021/acs.analchem.0c00985
  
   
• Yang, L., Garcia-Canaveras, J.C., Chen, Z., Wang, L., Liang, L., Jang, C., Mayr, J.A., Zhang, Z., Ghergurovich, J.M., Zhan, L., Joshi, S., Hu, Z., McReynolds, M.R., Su, X., White, E., Morscher, R.J., and J.D. Rabinowitz. (2020). Serine catabolism feeds NADH when respiration is impaired. Cell Metabolism. DOI: 10.1016/j.cmet.2020.02.017
  
   
• McReynolds, M.R., Chellappa, K. and J.A. Baur. (2020). Age-related NAD⁺ decline. Experimental Gerontology. DOI: 10.1016/j.exger.2020.110888
  
   
• McReynolds, M.R., Wang, W., Holleran, L.M. and W. Hanna-Rose. (2017). Uridine monophosphate synthetase enables eukaryotic de novo NAD⁺ biosynthesis from quinolinic acid. JBC. C117. 795344. DOI: 10.1074/jbc.C117.795344
  
   
• Ozcelik, A., Nama, N., Huang, PH., Kaynak, M., McReynolds, MR., Hanna-Rose, W., Huang, TJ. (2016). Acoustofluidic rotational manipulation of cells and organisms using oscillating solid structures. SMALL. DOI: 10.1002/smll.201601760
  
   
• Wang W., McReynolds M.R., Gonvalves, J.F., Shu, M., Dhondt, I., Braeckman, B.P., Lange, S.E., Kho, K. Detwiler, A.C., Pacella, M.J. and W. Hanna-Rose. (2015). Comparative metabolomic profiling reveals that dysregulated glycolysis stemming from lack of salvage NAD⁺ biosynthesis impairs reproductive development in C. elegans” J. Bio. Chem. 2015, 290:26163-26179.
  
   
• Crook, M., McReynolds, M., Wang, W., Hanna-Rose, W. (2014).  An NAD⁺ Biosynthetic Pathway Enzyme Functions Cell Non-Autonomously in C. elegans Development. Developmental Dynamics. 243:965-967.

Preprint server:

• Lakhina, V., McReynolds, M.R., Grimes, D.T., Rabinowitz, J.D., Burdine, R.D. and C.T. Murphy. (2019). ZIP-5/bZIP transcription factor regulation of folate metabolism is critical for aging axon regeneration. bioRxiv, 727719; doi: https://doi.org/10.1101/727719
  
   
• Fenton, A.R., Janowitz, H.N. McReynolds, M.R., Wang, W. and W. Hanna-Rose. (2017). A Caenorhabditis elegans model of adenylosuccinate lyase deficiency revels a neuromuscular and reproductive phenotypes of distinct etiology. bioRxiv, 181719.
  
   
• Change, S.M., McReynolds, M.R. and W. Hanna-Rose. (2017). Mitochondrial sirtuins sir-2.2 and sir-2.3 regulate lifespan in C. elegans. bioRxiv. 181727.

Commentaries/Opinion Pieces:

• Termini, C.M., Rutaganira, F.U.N., Palavicino-Maggio, C.B., Spriggs, C.S., Evans, C.S., M.R. McReynolds. Using virtual interviewing to develop a more efficient and robust hybrid academic job market. 2021. Cell. Accepted.
  
   
• Hinton Jr., A.O., Termini, C.M., Spencer, E.C., Rutaganira, F., Chery, D., Roby, R.S., Vue, Z., Pack, A.D., Brady, L.J., Garza-Lopez, E., Marshall, A., James, J.L., Shuler, H.D., Taylor, B.L., McReynolds, M.R.* and Palavicino-Maggio, C.B.* Patching the Leaks: Reimagining the STEM Pipeline. Cell. 2020 Oct 29;183(3):568-575. doi: 10.1016/j.cell.2020.09.029.
  
   
• Hinton Jr., A.O., McReynolds, M.R., Martinez, D., Shuler, H.D. and C.M. Termini. The Power of Saying No. EMBO Reports. https://doi.org/10.15252/embr.202050918
  
   
• Hinton Jr., A.O., Vue, Z., Termini, C.M., Taylor, B.L., Shuler, H.D. and M.R. McReynolds. Mentoring Minority Trainees in STEM. EMBO Reports.  https://doi.org/10.15252/embr.202051269
  
   
• McReynolds, M.R., Termini, C.M., Hinton Jr., A.O., Taylor, B.L., Vue, Z., Huang, S.C., Roby, R.S., Shuler, H.D. and C.S. Carter. The Art of Virtual Mentoring in the 21^st Century for STEM Majors and Beyond. Nature Biotechnology. DOI: 10.1038/s41587-020-00758-7.
  
   
• Termini, C.M.*, McReynolds, M.R.*, Rutaganira, F*., Roby, R.S., Carter, C.S., Huang, S.C., Vue, Z., Hinton Jr., A.O., Martinez, D., Shuler, H.D. and B.L. Taylor. Mentoring during Uncertain Times. Trends in Biomedical Science. https://doi.org/10.1016/j.tibs.2021.01.012