(Archived) Regulation of autophagy in development and disease

Summary

Autophagy is a cellular process to remove unneeded or damaged components. Effective Autophagy is essential for healthy cell function and development. The dysregulation of Autophagy contributes to a wide range of conditions, including cancer and degenerative diseases. I study the Autophagy pathway between normal and cancer cells derived from mouse models and human patients. By understanding the gene expression and interaction among key Autophagy regulators, we can identify the role of this process in the initiation and progression of diseases.

Autophagy and adipocyte differentiation

The main application in my research is the role of autophagy in developing the adipocyte phenotype and its connection to metabolic diseases. The following are some of the findings that came out of this work:

A hierarchical arrangement between adipogenic transcription factors and co-factors drives the regulation of autophagy during adipogenesis. (Paper)
Autophagy genes are regulated as part of the transcriptional programs through adipogenic factors. These regulators act either directly or indirectly through autophagy-specific transcription factors during adipogenesis. (Paper)
Adipogenic stimuli temporally and locally modulate AMPK-autophagy interaction. (Paper)
Autophagy removes intracellular components and supplies energy sources for lipid biogenesis during adipocyte differentiation. (Paper)
Preadipocytes are a mixture of different cells of which a limited fraction become mature adipocytes. (Paper)

These studies were mainly based on datasets I curated from publicly available high-throughput data.

A curated gene expression dataset of differentiating 3T3-L1 adipocytes under pharmacological and genetic perturbations. (Paper)
A curated data set to model gene expression and the DNA-binding in the 3T3-L1 differentiating adipocytes. (Paper)
A dataset of tissue-specific gene expression in obese hyperglycemic mice (Paper)

Autophagy and cancer

My other area of interest is the role Raf kinase inhibitor protein (RKIP) plays in cancer development. RKIP is a regulator of Autophagy in normal cells; the loss of RKIP in the prostate and breast cancer prompts the study of its downstream consequences. In collaboration with other lab members, we made a few observations related to this topic, which we reported in several publications.

A summary of the anti-metastatic effect of RKIP via modulating autophagy. (Book chapter)
RKIP interacts with EMT and autophagy as part of the same functional unit in developing prostate cancer. (Paper)
MTDH is a novel factor that controls the RKIP transcription, which is essential for cancer progression. (Paper)
A review of the cross-talk between autophagy and oncogenic signaling pathways and implications for cancer therapy. (Paper)

Publications

Hierarchical Regulation of Autophagy During Adipocyte Differentiation

Mahmoud Ahmed, Trang Huyen Lai, Trang Minh Pham, Sahib Zada, Omar Elashkar, Jin Seok Hwang, Deok Ryong Kim

PLoS ONE, vol. 17(1), 2022 6, pp. e0250865

A Small Fraction of Progenitors Differentiate Into Mature Adipocytes by Escaping the Constraints on the Cell Structure.

Mahmoud Ahmed, Trang Huyen Lai, Deok Ryong Kim

Frontiers in Cell and Developmental Biology, vol. 9, 2021 Sep 11

Cross talk between autophagy and oncogenic signaling pathways and implications for cancer therapy.

Sahib Zada, Jin Seok Hwang, Mahmoud Ahmed, Trang Huyen Lai, Trang Minh Pham, Omar Elashkar, Deok Ryong Kim

Biochimica et Biophysica Acta, vol. 1876(1), 2021 Apr 13, pp. 188565-188565

Transcriptional Repression of Raf Kinase Inhibitory Protein Gene by Metadherin during Cancer Progression.

Trang Huyen Lai, Mahmoud Ahmed, Jin Seok Hwang, Sahib Zada, Trang Minh Pham, Omar Elashkar, Deok Ryong Kim

International Journal of Molecular Sciences, vol. 22(6), 2021 Feb 17

Anti-cancer effect of RKIP via modulating autophagy during metastasis

Mahmoud Ahmed, Deok Ryong KIm

Prognostic and Therapeutic Applications of RKIP in Cancer, Benjamin Bonavida, Stavroula Baritaki, chapter 15, 1st ed., vol. 1, Academic Press, 2020, pp. 277-293

Curated gene expression dataset of differentiating 3T3-L1 adipocytes under pharmacological and genetic perturbations

Mahmoud Ahmed, Do Sik Min, Deok Ryong Kim

Adipocyte, vol. 9(1), 2020, pp. 600-608

Modelling the gene expression and the DNA-binding in the 3T3-L1 differentiating adipocytes.

Mahmoud Ahmed, Deok Ryong Kim

Adipocyte, vol. 8(1), 2019, pp. 401-411

Transcriptional Regulation of Autophagy Genes via Stage-Specific Activation of CEBPB and PPARG during Adipogenesis: A Systematic Study Using Public Gene Expression and Transcription Factor Binding Datasets

Mahmoud Ahmed, Trang Huyen Lai, Jin Seok Hwang, Sahib Zada, Trang Minh Pham, Deok Ryong Kim

Cells, vol. 8(11), 2019 Sep 25

Functional Linkage of RKIP to the Epithelial to Mesenchymal Transition and Autophagy during the Development of Prostate Cancer.

Mahmoud Ahmed, Trang Huyen Lai, Sahib Zada, Jin Seok Hwang, Trang Minh Pham, Miyong Yun, Deok Ryong Kim

Cancers, vol. 10(8), 2018 Jul 16

Co-Expression Network Analysis of AMPK and Autophagy Gene Products during Adipocyte Differentiation

Mahmoud Ahmed, Jin Seok Hwang, Trang Huyen Lai, Sahib Zada, Huynh Quoc Nguyen, Trang Min Pham, Miyong Yun, Deok Ryong Kim

International Journal of Molecular Sciences, vol. 19(6), 2018 May 19

Systematic characterization of autophagy-related genes during the adipocyte differentiation using public-access data.

Mahmoud Ahmed, Huynh Quoc Nguyen, Jin Seok Hwang, Sahib Zada, Trang Huyen Lai, Sang Soo Kang, Deok Ryong Kim

Oncotarget, vol. 9(21), 2018 Jan 15, pp. 15526-15541