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[Aug. 28] D5 seminar- Dr. Ralf Jauch (Hongkong University)

May 24 2024

The "D5 Medical & Life Science Seminar" course will be offered by International Research Center for Medical Sciences (IRCMS). It will run from May 2024 to March 2025, with lectures given by scientists who are affiliated with IRCMS or in collaboration with researchers at IRCMS. The lectures will be given once a month, in English, and by leading scientists in the relevant research field. Students will be taught: 1) how normal physiological functions are maintained in the human body; 2) how these systems become abnormal under certain pathophysiologic conditions; 3) why stem cells are important in animal development and homeostasis; 4) how stem cell-based approaches can help us understand disease mechanisms and find potential cure for diseases related to stem cell malfunction (e.g., cancer, aging).

Anyone who wants to join is welcome.
For students who have registered for the course, please check your attendance in Moodle.

Date      : August 28th, 2024 (Wednesday)

Format  : Hybrid

Time      : 16:00 - 17:00 (JST)

Speaker : Dr. Ralf Jauch (Hongkong University)

Title       : The directed and natural evolution of the molecular toolkit of stem cells

Abstract  :

Our team uses re-designed versions of SOX, OCT, and KLF transcription factors to reprogram somatic cells to induce multipotent, pluripotent, and expanded potential stem cells. Directed molecular evolution enabled the discovery of mutant factors with modified partnerships, new functions, and drastically boosted activity. For example, re-engineered SOX17 turns into an enhanced 'ultra-SOX', termed eSOX17, which speeds up pluripotency induction. In human cells, eSOX17 enables the direct conversion of somatic cells into cells with totipotency features. Two-factor eSOX17/c-MYC cocktails can directly transdifferentiate human blood into induced brain stem cells, avoiding the rejuvenation associated with pluripotency induction. These potentially 'old' stem cells open up possibilities to model and revert age-linked neurological pathologies. Inspired by the close partnership between SOX/OCT and the potential of re-engineered variants to program stem cell states, we have begun to study their evolutionary history. Until now, SOX and OCT factors have been believed to be unique to animals. Surprisingly, we discovered that key parts of the molecular toolkit essential for mammalian pluripotency emerged long before the evolution of animal multicellularity and the existence of stem cells as we know them today.




Dr. Ralf Jauch relocated to Hong Kong in 2018 as an Associate Professor at the School of Biomedical Sciences of HKUMed, where he leads a multidisciplinary research program at the interface of protein engineering and stem cell biology. He is known for his contributions to improving the quality, utility, and efficiency of stem cell generation through the re-engineering of pioneer transcription factors. Dr. Jauch published 81 articles that are cited 4200 times (H-index: 40). He completed his undergraduate studies at the Universities of Jena, Germany, and Manchester, UK, and obtained his Ph.D. at the International Max Planck Research School in Göttingen. In 2006, he moved to Asia to join the Genome Institute of Singapore where he developed a passion for stem cells and protein design. In 2013, he joined the Guangzhou Institute of Biomedicine and Health as Principal Investigator where he established the GIBH- Max Planck Center for Regenerative Medicine and served as its deputy director. Throughout his career, Dr. Jauch filed seven patents including a recent non-provisional patent with the Centre for Translational Stem Cell Biology  (Health@InnoHK).

10 most significant publications since the first appointment at HKU in 2018:

1      Malik V, Glaser LV, Zimmer D, Velychko S, Weng M, Holzner M, Arend M, Chen Y, Srivastava Y, Veerapandian V, Shah Z, Esteban MA, Wang H, Chen J, Scholer HR, Hutchins AP, Meijsing SH, Pott S, Jauch R (2019) Pluripotency reprogramming by competent and incompetent POU factors uncovers temporal dependency for Oct4 and Sox2. Nat Commun 10: 3477.

2      Hu H, Ho DHH, Tan DS, MacCarthy CM, Yu CH, Weng M, Scholer HR, Jauch R (2023) Evaluation of the determinants for improved pluripotency induction and maintenance by engineered SOX17. Nucleic Acids Res 51: 8934-8956.

3      Weng M, Hu H, Graus MS, Tan DS, Gao Y, Ren S, Ho DHH, Langer J, Holzner M, Huang Y, Ling GS, Lai CSW, Francois M, Jauch R (2023) An engineered Sox17 induces somatic to neural stem cell fate transitions independently from pluripotency reprogramming. Sci Adv 9: eadh2501.

4      Tan DS, Cheung SL, Gao Y, Weinbuch M, Hu H, Shi L, Ti SC, Hutchins AP, Cojocaru V, Jauch R (2023) The homeodomain of Oct4 is a dimeric binder of methylated CpG elements. Nucleic Acids Res 51: 1120-1138.

5      MacCarthy CM, Wu G, Malik V, Menuchin-Lasowski Y, Velychko T, Keshet G, Fan R, Bedzhov I, Church GM, Jauch R, Cojocaru V, Scholer HR, Velychko S (2024) Highly cooperative chimeric super-SOX induces naive pluripotency across species. Cell Stem Cell 31: 127-147 e9.

6      Tan DS, Chen Y, Gao Y, Bednarz A, Wei Y, Malik V, Ho DH, Weng M, Ho SY, Srivastava Y, Velychko S, Yang X, Fan L, Kim J, Graumann J, Stormo GD, Braun T, Yan J, Scholer HR, Jauch R (2021) Directed Evolution of an Enhanced POU Reprogramming Factor for Cell Fate Engineering. Mol Biol Evol 38: 2854-2868.

7      Hou L, Wei Y, Lin Y, Wang X, Lai Y, Yin M, Chen Y, Guo X, Wu S, Zhu Y, Yuan J, Tariq M, Li N, Sun H, Wang H, Zhang X, Chen J, Bao X, Jauch R (2020) Concurrent binding to DNA and RNA facilitates the pluripotency reprogramming activity of Sox2. Nucleic Acids Res 48: 3869-3887

8      Arruabarrena-Aristorena A, Maag JLV, Kittane S, Cai Y, Karthaus WR, Ladewig E, Park J, Kannan S, Ferrando L, Cocco E, Ho SY, Tan DS, Sallaku M, Wu F, Acevedo B, Selenica P, Ross DS, Witkin M, Sawyers CL, Reis-Filho JS, Verma S, Jauch R, Baselga J, Razavi P, Toska E, Scaltriti M. (2020) FOXA1 Mutations Reveal Distinct Chromatin Profiles and Influence Therapeutic Response in Breast Cancer. Cancer Cell 38: 534-550 e9 .

9      Wang X, Srivastava Y, Jankowski A, Malik V, Wei Y, Del Rosario RC, Cojocaru V, Prabhakar S, Jauch R (2018) DNA-mediated dimerization on a compact sequence signature controls enhancer engagement and regulation by FOXA1. Nucleic Acids Res 46: 5470-5486

10   Veerapandian V, Ackermann JO, Srivastava Y, Malik V, Weng M, Yang X, Jauch R (2018) Directed Evolution of Reprogramming Factors by Cell Selection and Sequencing. Stem Cell Reports 11: 593-606.

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