Dr. Mostafa Bakhti
Beta Cell Development and Regeneration
We study the programs underlying pancreatic endocrine formation and function to design novel strategies for diabetes therapy and tissue engineering. Towards this goal, we employ cutting-edge methods of mouse genetics, stem cell differentiation, 3D organoids, microscopy, multi-omics and gene editing to explore the cellular and molecular processes that coordinate endocrine cell morphogenesis, differentiation, and function.
Research Topics
Changying (Diana) Jing - PhD student
Understanding the basic principles of pancreatic endocrine lineage formation helps to design novel regenerative and cell-replacement approaches for diabetes treatment. Therefore, it is important to decode the mechanisms of lineage priming, specification and determination that produce different pancreatic endocrine subtypes (α-, β-, δ- and PP cells) in vivo. We use high-throughput transcriptomic and epigenetic profiling of endocrine progenitors to decipher endocrine lineage segregation. The outcome will provide deeper insight into endocrinogenesis for improved in vitro stem cell differentiation and in vivo regeneration strategies.
Perla Cota - PhD student
Lama Saber - PhD student
It is known that all pancreatic endocrine cell types are derived from endocrine progenitors. However, the molecular mechanisms that prime human endocrine progenitors and differentiate them into endocrine cells remain largely obscure. We employ cutting-edge technologies of stem cell differentiation and gene editing to study human endocrine lineage allocation. We use human induced pluripotent stem cells (iPSCs) and differentiate them towards the endocrine lineage through a multistep differentiation procedure. Using this modeling system, we identify novel players regulating different steps of human endocrinogenesis. The outcome will help to generate islet biomimetics with improved cell composition and function for cell-replacement therapy.
Oliver Czarnecki - PhD student
Pancreatic islets of Langerhans contain different hormone-producing endocrine cells (α-, β-, δ- and PP cells), which regulate glucose homeostasis. During embryonic development endocrine lineage segregation coupled with tissue morphogenesis generate islets. However, the underlying programs are not well characterized. We combine mouse genetics, 3D organoids and cell biology to dissect which cellular processes orchestrate morphogenetic events regulating endocrine cell egression and islet morphogenesis. The outcome will help to generate stem cell derived-islet biomimetics for cell-replacement but may also provide novel target to treat pancreatic diseases such pancreatic cancer.
Aimee Bastidas-Ponce - Postdoc
Jessica Jaki - Technical assistant
Restoring the glucose-stimulated insulin secretion (GSIS) potential of dysfunctional β-cells will not only ameliorate hyperglycemic condition, but also lead to rebuilding islet cell mass in patients with type 2 diabetes (T2D). Therefore, a better understanding of the underlying machineries of insulin trafficking and release will help to design novel therapeutic approaches for diabetes treatment. Several protein families, including Synaptotagmins (Syts), have been identified to coordinate insulin secretion. The misexpression of the atypical Ca2+-independent SYT13 in islets from patients with T2D has been reported. Yet, the functional impact of this protein on β-cells is not well understood. We combine islet biology with cutting-edge technologies of mouse genetic and multi-omics to explore the molecular action of Syt13 in β-cells. The outcome will help to uncover new targets or pathways to restore β-cell function.
PhD student - Beta cell development and regeneration
PhD Student - Beta cell development and regeneration
PhD student - Beta Cell Development and Regeneration
TA - Beta cell development and regeneration
Publications
Klein, D. ; Palla, G. ; Lange, M. ; Klein, M. ; Piran, Z. ; Gander, M. ; Meng-Papaxanthos, L. ; Sterr, M. ; Saber, L. ; Jing, C. ; Bastidas-Ponce, A. ; Cota, P. ; Tarquis Medina, M. ; Parikh, S. ; Gold, I. ; Lickert, H. ; Bakhti, M. ; Nitzan, M. ; Cuturi, M.C. ; Theis, F.J.
Mapping cells through time and space with moscot.Ansarullah ; Migliorini, A. ; Bakhti, M.
Editorial: Islet cell development, heterogeneity and regeneration.Akindehin, S.E. ; Liskiewicz, A. ; Liskiewicz, D. ; Bernecker, M. ; García-Cáceres, C. ; Drucker, D.J. ; Finan, B. ; Grandl, G. ; Gutgesell, R.M. ; Hofmann, S.M. ; Khalil, A. ; Liu, X. ; Cota, P. ; Bakhti, M. ; Czarnecki, O. ; Bastidas-Ponce, A. ; Lickert, H. ; Kang, L. ; Maity-Kumar, G. ; Novikoff, A. ; Parlee, S. ; Pathak, E. ; Schriever, S.C. ; Sterr, M. ; Ussar, S. ; Zhang, Q. ; DiMarchi, R. ; Tschöp, M.H. ; Pfluger, P.T. ; Douros, J.D. ; Müller, T.D.
Loss of GIPR in LEPR cells impairs glucose control by GIP and GIP:GLP-1 co-agonism without affecting body weight and food intake in mice.Cota, P. ; Caliskan, Ö.S. ; Bastidas-Ponce, A. ; Jing, C. ; Jaki, J. ; Saber, L. ; Czarnecki, O. ; Taskin, D. ; Blöchinger, A. ; Kurth, T. ; Sterr, M. ; Burtscher, I. ; Krahmer, N. ; Lickert, H. ; Bakhti, M.
Insulin regulates human pancreatic endocrine cell differentiation in vitro.Liskiewicz, A. ; Khalil, A. ; Liskiewicz, D. ; Novikoff, A. ; Grandl, G. ; Maity-Kumar, G. ; Gutgesell, R.M. ; Bakhti, M. ; Bastidas-Ponce, A. ; Czarnecki, O. ; Makris, K. ; Lickert, H. ; Feuchtinger, A. ; Tost, M. ; Coupland, C. ; Ständer, L. ; Akindehin, S.E. ; Prakash, S. ; Abrar, F. ; Castelino, R.L. ; He, Y. ; Knerr, P.J. ; Yang, B. ; Hogendorf, W.F.J. ; Zhang, S. ; Hofmann, S.M. ; Finan, B. ; DiMarchi, R.D. ; Tschöp, M.H. ; Douros, J.D. ; Müller, T.D.
Glucose-dependent insulinotropic polypeptide regulates body weight and food intake via GABAergic neurons in mice.Cota, P. ; Saber, L. ; Taskin, D. ; Jing, C. ; Bastidas-Ponce, A. ; Vanheusden, M. ; Shahryari, A. ; Sterr, M. ; Burtscher, I. ; Bakhti, M. ; Lickert, H.
NEUROD2 function is dispensable for human pancreatic β cell specification.Hrovatin, K. ; Bastidas-Ponce, A. ; Bakhti, M. ; Zappia, L. ; Büttner, M. ; Salinno, C. ; Sterr, M. ; Böttcher, A. ; Migliorini, A. ; Lickert, H. ; Theis, F.J.
Delineating mouse β-cell identity during lifetime and in diabetes with a single cell atlas.Quarta, C. ; Stemmer, K. ; Novikoff, A. ; Yang, B. ; Klingelhuber, F. ; Harger, A. ; Bakhti, M. ; Bastidas-Ponce, A. ; Baugé, E. ; Campbell, J.E. ; Capozzi, M.E. ; Clemmensen, C. ; Collden, G. ; Cota, P. ; Douros, J. ; Drucker, D.J. ; Dubois, B. ; Feuchtinger, A. ; García-Cáceres, C. ; Grandl, G. ; Hennuyer, N. ; Herzig, S. ; Hofmann, S.M. ; Knerr, P.J. ; Kulaj, K. ; Lalloyer, F. ; Lickert, H. ; Liskiewicz, A. ; Liskiewicz, D. ; Maity-Kumar, G. ; Perez-Tilve, D. ; Prakash, S. ; Sanchez-Garrido, M.A. ; Zhang, Q. ; Staels, B. ; Krahmer, N. ; DiMarchi, R.D. ; Tschöp, M.H. ; Finan, B. ; Müller, T.D.
GLP-1-mediated delivery of tesaglitazar improves obesity and glucose metabolism in male mice.Bakhti, M. ; Bastidas-Ponce, A. ; Tritschler, S. ; Czarnecki, O. ; Tarquis Medina, M. ; Nedvedova, E. ; Jaki, J. ; Willmann, S. ; Scheibner, K. ; Cota, P. ; Salinno, C. ; Boldt, K. ; Horn, N. ; Ueffing, M. ; Burtscher, I. ; Theis, F.J. ; Coskun, Ü. ; Lickert, H.
Synaptotagmin-13 orchestrates pancreatic endocrine cell egression and islet morphogenesis.Lange, M. ; Bergen, V. ; Klein, M. ; Setty, M. ; Reuter, B. ; Bakhti, M. ; Lickert, H. ; Ansari, M. ; Schniering, J. ; Schiller, H. B. ; Pe'er, D. ; Theis, F.J.
CellRank for directed single-cell fate mapping.Bakhti, M. ; Lickert, H.
New insights into β-cell failure, regeneration and replacement.Tarquis Medina, M. ; Scheibner, K. ; Gonzales García, I. ; Bastidas-Ponce, A. ; Sterr, M. ; Jaki, J. ; Schirge, S. ; García-Cáceres, C. ; Lickert, H. ; Bakhti, M.
Synaptotagmin-13 is a neuroendocrine marker in brain, intestine and pancreas.Chhabra, N.F. ; Amend, A.-L. ; Bastidas-Ponce, A. ; Sabrautzki, S. ; Tarquis Medina, M. ; Sachs, S. ; Rubey, M. ; Lorenz-Depiereux, B. ; Feuchtinger, A. ; Bakhti, M. ; Lickert, H. ; Przemeck, G.K.H. ; Hrabě de Angelis, M.
A point mutation in the Pdia6 gene results in loss of pancreatic β-cell identity causing overt diabetes.Nasteska, D. ; Fine, N.H.F. ; Ashford, F.B. ; Cuozzo, F. ; Viloria, K. ; Smith, G. ; Dahir, A. ; Dawson, P.W.J. ; Lai, Y.C. ; Bastidas-Ponce, A. ; Bakhti, M. ; Rutter, G.A. ; Fiancette, R. ; Nano, R. ; Piemonti, L. ; Lickert, H. ; Zhou, Q. ; Akerman, I. ; Hodson, D.J.
Author Correction: PDX1LOW MAFALOW β-cells contribute to islet function and insulin release.Alboushi, L. ; Hackett, A.P. ; Naeli, P. ; Bakhti, M. ; Jafarnejad, S.M.
Multifaceted control of mRNA translation machinery in cancer.Salinno, C. ; Büttner, M. ; Cota, P. ; Tritschler, S. ; Tarquis-Medina, M. ; Bastidas-Ponce, A. ; Scheibner, K. ; Burtscher, I. ; Böttcher, A. ; Theis, F.J. ; Bakhti, M. ; Lickert, H.
CD81 marks immature and dedifferentiated pancreatic β-cells.Burtscher, I. ; Tarquis Medina, M. ; Schirge, S. ; Beckenbauer, J. ; Bakhti, M. ; Lickert, H.
Generation of a novel nkx6-1 venus fusion reporter mouse line.Nasteska, D. ; Fine, N.H.F. ; Ashford, F.B. ; Cuozzo, F. ; Viloria, K. ; Smith, G. ; Dahir, A. ; Dawson, P.W.J. ; Lai, Y.C. ; Bastidas-Ponce, A. ; Bakhti, M. ; Rutter, G.A. ; Fiancette, R. ; Nano, R. ; Piemonti, L. ; Lickert, H. ; Zhou, Q. ; Akerman, I. ; Hodson, D.J.
PDX1LOW MAFALOW β-cells contribute to islet function and insulin release.Zhang, Q. ; Delessa, C.T. ; Augustin, R. ; Bakhti, M. ; Collden, G. ; Drucker, D.J. ; Feuchtinger, A. ; García-Cáceres, C. ; Grandl, G. ; Harger, A. ; Herzig, S. ; Hofmann, S.M. ; Holleman, C.L. ; Jastroch, M. ; Keipert, S. ; Kleinert, M. ; Knerr, P.J. ; Kulaj, K. ; Legutko, B. ; Lickert, H. ; Liu, X. ; Luippold, G. ; Lutter, D. ; Malogajski, E. ; Tarquis Medina, M. ; Mowery, S.A. ; Blutke, A. ; Perez-Tilve, D. ; Salinno, C. ; Sehrer, L. ; DiMarchi, R.D. ; Tschöp, M.H. ; Stemmer, K. ; Finan, B. ; Wolfrum, C. ; Müller, T.D.
The glucose-dependent insulinotropic polypeptide (GIP) regulates body weight and food intake via CNS-GIPR signaling.Contact