Chelsea Nnebe

All Publications

• New Insights Into Diabetes-Induced Cell-Type-Specific Responses in the Neural Retina via Single-Cell Transcriptomics: A Report on Research Supported by Pathway to Stop Diabetes. Diabetes Deng, B., Nnebe, C., Prakhar, P., Ren, X., Sun, D., Sun, Y., Wang, S. 2025

  Abstract

  Single-cell transcriptomics provides a powerful solution for dissecting diabetes-induced cell-type-specific responses in mammalian retina. This article summarizes key findings from recent single-cell transcriptomic studies regarding the mechanisms of diabetic retinopathy, with a particular emphasis on the neural retina. Specific retinal neuronal types/subtypes exhibit heightened sensitivity to diabetes at the transcriptional level. Retinal Müller glial cells are key contributors to diabetic retinopathy and promising therapeutic targets for retinal protection against diabetes.

  View details for DOI 10.2337/dbi24-0009

  View details for PubMedID 40794446

• miR-193b-365 microcluster downstream ofFezf2coordinates neuron-subtype identity and dendritic morphology in cortical projection neurons. iScience Iyer, A., Vaasjo, L. O., Siththanandan, V. B., K C, R., Thurmon, A., Akumuo, M., Lu, V., Nnebe, C., Nair, R., Galazo, M. J., Tharin, S. 2024; 27 (12): 111500

  Abstract

  Different neuron types develop characteristic axonal and dendritic arborizations that determine their inputs, outputs, and functions. Expression of fate-determinant transcription factors is essential for specification of their distinct identities. However, the mechanisms downstream of fate-determinant factors coordinating different aspects of neuron identity are not understood. Specifically, how distinct projection neurons develop appropriate dendritic arbors that determine their inputs is unknown. Here, we investigate this question in corticospinal and callosal projection neurons. We identified a mechanism linking the corticospinal/corticofugal identity gene Fezf2 with the regulation of dendritic development. We show that miR-193b365 microRNA cluster is regulated by Fezf2 and enriched in corticospinal neurons. miR-193b365 represses mitogen-activated protein kinase 8 (MAPK8) to regulate corticospinal dendritic development. miR-193b365 overexpression in callosal neurons abnormally reduces MAPK8 signal and dendritic complexity. Our findings show that regulation of MAPK8 via miR-193b365 cluster regulates dendritic development, providing a mechanism that coordinates projection neuron identity, specified by Fezf2, and neuron-specific dendritic morphology.

  View details for DOI 10.1016/j.isci.2024.111500

  View details for PubMedID 39759000

• Challenges and advice for MD/PhD applicants who are underrepresented in medicine. Molecular biology of the cell Bannerman, C. n., Guzman, N. n., Kumar, R. n., Nnebe, C. n., Setayesh, J. n., Venapally, A. n., Sussman, J. H. 2020; 31 (24): 2640–43

  Abstract

  The importance of diversity is self-evident in medicine and medical research. Not only does diversity result in more impactful scientific work, but diverse teams of researchers and clinicians are necessary to address health disparities and improve the health of underserved communities. MD/PhD programs serve an important role in training physician-scientists, so it is critical to ensure that MD/PhD students represent diverse backgrounds and experiences. Groups who are underrepresented in medicine and the biomedical sciences include individuals from certain racial and ethnic backgrounds, individuals with disabilities, individuals from disadvantaged backgrounds, and women. However, underrepresented students are routinely discouraged from applying to MD/PhD programs due to a range of factors. These factors include the significant cost of applying, which can be prohibitive for many students, the paucity of diverse mentors who share common experiences, as well as applicants' perceptions that there is inadequate support and inclusion from within MD/PhD programs. By providing advice to students who are underrepresented in medicine and describing steps programs can take to recruit and support minority applicants, we hope to encourage more students to consider the MD/PhD career path that will yield a more productive and equitable scientific and medical community.

  View details for DOI 10.1091/mbc.E20-07-0444

  View details for PubMedID 33180675

• Fatostatin inhibits cancer cell proliferation by affecting mitotic microtubule spindle assembly and cell division. The Journal of biological chemistry Gholkar, A. A., Cheung, K. n., Williams, K. J., Lo, Y. C., Hamideh, S. A., Nnebe, C. n., Khuu, C. n., Bensinger, S. J., Torres, J. Z. 2016

  Abstract

  The sterol regulatory element binding protein (SREBP) transcription factors have become attractive targets for pharmacological inhibition in the treatment of metabolic diseases and cancer. SREBPs are critical for the production and metabolism of lipids and cholesterol, which are essential for cellular homeostasis and cell proliferation. Fatostatin was recently discovered as a specific inhibitor of SCAP (SREBP cleavage-activating protein), which is required for SREBP activation. Fatostatin possesses antitumor properties including the inhibition of cancer cell proliferation, invasion and migration, and it arrests cancer cells in G2/M phase. Although Fatostatin has been viewed as an antitumor agent due to its inhibition of SREBP and its effect on lipid metabolism, we show that Fatostatin's anticancer properties can also be attributed to its inhibition of cell division. We analyzed the effect of SREBP activity inhibitors including Fatostatin, PF-429242 and Betulin on the cell cycle and determined that only Fatostatin possessed antimitotic properties. Fatostatin inhibited Tubulin polymerization, arrested cells in mitosis, activated the spindle assembly checkpoint and triggered mitotic catastrophe and reduced cell viability. Thus Fatostatin's ability to inhibit SREBP activity and cell division could prove beneficial in treating aggressive types of cancers like glioblastomas that have elevated lipid metabolism, fast proliferation rates and often develop resistance to current anticancer therapies.

  View details for DOI 10.1074/jbc.C116.737346

  View details for PubMedID 27378817