Article
Cell & Tissue Engineering
Seong-Min Kim, Eun-Ji Kwon, Yun-Jeong Kim, Young-Hyun Go, Ji-Young Oh, Seokwoo Park, Jeong Tae Do, Keun-Tae Kim, Hyuk-Jin Cha
Summary: This study discovered the differential roles of Shp2 in naive and primed pluripotency and proposed the usage of iShp2 instead of iMek1 for the efficient maintenance and establishment of naive pluripotency.
STEM CELL RESEARCH & THERAPY
(2022)
Article
Oncology
Anamarija Pfeiffer, Giulia Franciosa, Marie Locard-Paulet, Ilaria Piga, Kristian Reckzeh, Vidyasiri Vemulapalli, Stephen C. Blacklow, Kim Theilgaard-Monch, Lars J. Jensen, Jesper V. Olsen
Summary: The protein tyrosine phosphatase SHP2 plays a crucial role in the oncogenic transformation of AML cells. By stabilizing SHP2 in its autoinhibited conformation, allosteric inhibitors show promise in inhibiting the RAS-ERK pathway and preventing cell proliferation and survival. Combination therapies that target SHP2 and other key enzymes can prevent the development of resistance.
Article
Medicine, Research & Experimental
Mojdeh Abbasi, Vivek K. Gupta, Nitin Chitranshi, Veer Gupta, Reza Ranjbaran, Rashi Rajput, Kanishka Pushpitha, K. B. Devaraj, Yuyi You, Ghasem Hosseini Salekdeh, Robert G. Parton, Mehdi Mirzaei, Stuart L. Graham
Summary: The study shows that silencing of Shp2 has protective effects on RGCs in glaucomatous conditions, and this protection is dependent on Cav-1, suggesting interactions between these two proteins in the retina which result in improvements in inner retinal function and structure.
Article
Chemistry, Medicinal
Sara Bobone, Luca Pannone, Barbara Biondi, Maja Solman, Elisabetta Flex, Viviana Claudia Canale, Paolo Calligari, Chiara De Faveri, Tommaso Gandini, Andrea Quercioli, Giuseppe Torini, Martina Venditti, Antonella Lauri, Giulia Fasano, Jelmer Hoeksma, Valerio Santucci, Giada Cattani, Alessio Bocedi, Giovanna Carpentieri, Valentina Tirelli, Massimo Sanchez, Cristina Peggion, Fernando Formaggio, Jeroen den Hertog, Simone Martinelli, Gianfranco Bocchinfuso, Marco Tartaglia, Lorenzo Stella
Summary: A new class of inhibitors targeting protein-protein interactions of the SHP2 phosphatase were developed, showing potential for cancer and rare disease therapy. These inhibitors exhibit high affinity and selectivity, with stronger affinity for pathogenic SHP2 mutants. The best peptide inhibitor demonstrated promising effects in zebrafish embryos, indicating a novel route for SHP2-targeted therapies and further research into protein-protein interactions in SHP2 function.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Dhanya Raveendra-Panickar, Darren Finlay, Fabiana Izidro Layng, Lester J. Lambert, Maria Celeridad, Ming Zhao, Karina Barbosa, Laurent J. S. De Backer, Elizabeth Kwong, Palak Gosalia, Socorro Rodiles, John Holleran, Robert Ardecky, Stefan Grotegut, Steven Olson, John H. Hutchinson, Elena B. Pasquale, Kristiina Vuori, Aniruddha J. Deshpande, Nicholas D. P. Cosford, Lutz Tautz
Summary: Disturbance of the balance between tyrosine phosphorylation and dephosphorylation controlled by protein tyrosine kinases and protein tyrosine phosphatases (PTPs) can lead to cancer development. PTPs, which have long been considered undruggable, are now gaining attention in drug discovery. One PTP target is SHP2, which is involved in tumor initiation, progression, metastasis, and treatment resistance. This study reports the discovery of novel furanylbenzamide molecules as inhibitors of both WT and oncogenic SHP2, showing potential as therapeutic targets for cancer treatment.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Genetics & Heredity
Rebeca Lorca, Luca Pannone, Elias Cuesta-Llavona, Gianfranco Bocchinfuso, Julian Rodriguez-Reguero, Giovanna Carpentieri, Ines Hernando, Elisabetta Flex, Marco Tartaglia, Eliecer Coto, Juan Gomez, Simone Martinelli
Summary: The RASopathies are a group of clinically related disorders caused by mutations affecting genes participating in the RAS-MAPK signaling cascade, with PTPN11 gene mutations being associated with Noonan syndrome and Noonan syndrome with multiple lentigines. This study reported a patient with Noonan syndrome carrying biallelic variants in the PTPN11 gene, with one previously reported mutation and one novel catalytic impairment mutation.
Article
Ophthalmology
Matthew M. Harper, Erin A. Boese, Randy H. Kardon, Johannes Ledolter, Markus H. Kuehn
Summary: There was no significant difference in the expression of BDNF and TrkB between glaucomatous and control retinas, but BDNF expression was associated with the use of prostaglandin analogs, while TrkB expression was correlated with factors such as intraocular pressure, drug usage, and treatment outcomes.
CURRENT EYE RESEARCH
(2021)
Article
Hematology
Yuhan Yan, Lei Dong, Chao Chen, Kevin D. Bunting, Qianjin Li, Elliot Stieglitz, Mignon L. Loh, Cheng-Kui Qu
Summary: Suppression of normal blood cell development is observed in juvenile myelomonocytic leukemia (JMML), impacting therapeutic outcomes. In a study, the most common mutation found in JMML (Ptpn11(E76K)) was induced specifically in the myeloid lineage, leading to the development of a JMML-like myeloproliferative neoplasm (MPN). Importantly, hematopoietic stem cells (HSCs) in the same bone marrow microenvironment were aberrantly activated and differentiated, resulting in loss of quiescence and exhaustion. Further experiments showed that JMML/MPN cells accelerated differentiation in normal hematopoietic stem/progenitor cells. Excessive production of IL-1 beta by Ptpn11(E76K/+) MPN cells was identified and depletion of the IL-1 beta receptor restored HSC quiescence and rescued them from exhaustion, suggesting IL-1 beta signaling as a potential therapeutic target for preserving normal hematopoietic development in JMML.
Article
Cell Biology
Wendy S. Chen, Yan Liang, Min Zong, Jacey J. Liu, Kota Kaneko, Kaisa L. Hanley, Kun Zhang, Gen-Sheng Feng
Summary: The mechanisms of Myc-driven liver tumorigenesis involve complex interactions between cell-intrinsic oncogenic signaling and a tumor-promoting microenvironment generated by disrupting specific oncogenic pathways. While Myc-induced tumors are aggravated in mice with hepatocyte-specific Ptpn11/Shp2 deletion, the development of tumors selectively from Shp2-positive hepatocytes in Shp2-deficient liver highlights the crucial role of Shp2 in promoting Ras-Erk signaling and sustaining Myc stability. Despite a stringent requirement of Shp2 cell autonomously, its deletion induces an immunosuppressive environment leading to defective clearance of tumor-initiating cells and aggressive tumor progression. Additionally, upregulation of basal Wnt/beta-catenin signaling in Shp2-deficient liver further augmented by Myc transfection underscores the essential role of beta-catenin in Myc-induced HCC progression.
Article
Biochemistry & Molecular Biology
Eun-Jung Yoon, Yunseo Choi, Dongsun Park
Summary: This study investigated the effects of transplantation of choline acetyltransferase (ChAT)-overexpressing neural stem cells on learning and memory in ovariectomized rats. The results showed that the transplantation increased the levels of brain-derived neurotrophic factor (BDNF) and nerve-growth factor (NGF), improved memory deficit, and upregulated the expression of estrogen receptors (ERs) and the cholinergic system in the brains of ovariectomized animals. The findings suggest that this transplantation may ameliorate cognitive impairments caused by estradiol loss or reduction.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Romain J. Amante, Priska Auf Der Maur, Veronica Richina, Atul Sethi, Vytautas Iesmantavicius, Debora Bonenfant, Nicola Aceto, Mohamed Bentires-Alj
Summary: This study reveals that SHP2 mediates breast cancer progression by enhancing the production and secretion of the pro-metastatic cytokine IL-8. Mechanistic insights into the effects of SHP2 inhibition and its downstream repercussions are also provided. These results support a rationale for targeting SHP2 in breast cancer treatment.
JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA
(2022)
Article
Neurosciences
Sudhirkumar Yanpallewar, Gianluca Fulgenzi, Francesco Tomassoni-Ardori, Colleen Barrick, Lino Tessarollo
Summary: The pathophysiology of ALS, caused by motoneuron degeneration, is largely unknown. Insufficient neurotrophic support has been suggested as one of the causes of motoneuron cell death. Deleting the BDNF receptor TrkB.T1 in ALS animal models delays cell death and muscle weakness, but does not affect the inflammatory state in the mutant spinal cord.
EXPERIMENTAL NEUROLOGY
(2021)
Article
Chemistry, Medicinal
Barbara Czako, Yuting Sun, Timothy McAfoos, Jason B. Cross, Paul G. Leonard, Jason P. Burke, Christopher L. Carroll, Ningping Feng, Angela L. Harris, Yongying Jiang, Zhijun Kang, Jeffrey J. Kovacs, Pijus Mandal, Brooke A. Meyers, Faika Mseeh, Connor A. Parker, Simon S. Yu, Christopher C. Williams, Qi Wu, Maria Emilia Di Francesco, Giulio Draetta, Timothy Heffernan, Joseph R. Marszalek, Nancy E. Kohl, Philip Jones
Summary: The search for potent compounds interfering with the function of SHP2 led to the discovery of a series of pyrimidinone compounds with high potency and narrow hERG window in humans, showing potential for targeted therapies in cancers driven by RTK and KRAS mutations.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Oncology
Hirohisa Kano, Eiki Ichihara, Hiromi Watanabe, Kazuya Nishii, Chihiro Ando, Takamasa Nakasuka, Kiichiro Ninomiya, Yuka Kato, Toshio Kubo, Kammei Rai, Kadoaki Ohashi, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura
Summary: This study found the potential role of SHP2 in residual cells of NSCLC with ALK/ROS1/EGFR alterations, and showed that combining SHP2 inhibitor SHP099 with molecular-targeted therapy can effectively inhibit cancer cell growth.
MOLECULAR CANCER THERAPEUTICS
(2021)
Article
Biochemistry & Molecular Biology
Carolina Villarroya-Beltri, Ana Filipa B. Martins, Alejandro Garcia, Daniel Gimenez, Eduardo Zarzuela, Monica Novo, Cristina Del Alamo, Jose Gonzalez-Martinez, Gloria C. Bonel-Perez, Irene Diaz, Maria Guillamot, Massimo Chiesa, Ana Losada, Osvaldo Grana-Castro, Meritxell Rovira, Javier Munoz, Maria Salazar-Roa, Marcos Malumbres
Summary: Maintenance of stemness is regulated by CDC14, a CDK-counteracting phosphatase, which dephosphorylates UTF1 to trigger its degradation and control neural differentiation. Lack of CDC14 results in deficient neural system development and impaired neural differentiation from ESCs. CDC14 phosphatases are critical molecular switches linking cell cycle regulation and self-renewal.
Article
Neurosciences
Yanuar Alan Sulistio, Han Kyu Lee, Sung Jun Jung, Klaus Heese
MOLECULAR NEUROBIOLOGY
(2018)
Article
Oncology
Chinmay Satish Rahane, Arne Kutzner, Klaus Heese
JOURNAL OF NEURO-ONCOLOGY
(2019)
Article
Oncology
Chinmay Satish Rahane, Arne Kutzner, Klaus Heese
Article
Neurosciences
Nguyen Thi Thanh Ho, Arne Kutzner, Klaus Heese
MOLECULAR NEUROBIOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Naresh Poondla, Arun Pandian Chandrasekaran, Klaus Heese, Kye-Seong Kim, Suresh Ramakrishna
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2019)
Article
Multidisciplinary Sciences
Markus Schmidt, Klaus Heese, Arne Kutzner
NATURE COMMUNICATIONS
(2019)
Article
Chemistry, Medicinal
Subrata Pramanik, Manisha Thaker, Ananda Gopu Perumal, Rajasekaran Ekambaram, Naresh Poondla, Markus Schmidt, Pok-Son Kim, Arne Kutzner, Klaus Heese
MOLECULAR INFORMATICS
(2020)
Article
Microbiology
Raja Mohan Gopalakrishnan, Tamilvendan Manavalan, Janani Ramesh, Kalaichelvan Puthupalayam Thangavelu, Klaus Heese
Review
Integrative & Complementary Medicine
Klaus Heese
EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE
(2020)
Article
Biology
Tamilvendan Manavalan, Arulmani Manavalan, Shiyamsundar Ramachandran, Klaus Heese
Review
Oncology
Nguyen Thi Thanh Ho, Chinmay Satish Rahane, Subrata Pramanik, Pok-Son Kim, Arne Kutzner, Klaus Heese
Summary: This review discusses the significance of the gene pair |-SRGAP2-FAM72-| in the treatment of GBM and other cancers, as well as the potential of neural stem cells in regenerative medicine. It highlights the role of the SRGAP2-Family with sequence similarity 72 (FAM72) master gene in cell renewal and differentiation, emphasizing the importance of monitoring this gene for cancer prevention and treatment.
Article
Chemistry, Multidisciplinary
Senthil Renganathan, Sakthivel Manokaran, Preethi Vasanthakumar, Usha Singaravelu, Pok-Son Kim, Arne Kutzner, Klaus Heese
Summary: This study identified bioactive constituents in Leucaena leucocephala leaves using gas chromatography-mass spectrometry, and found that certain compounds could potentially be used as antidiabetic agents.
Article
Oncology
Senthil Renganathan, Subrata Pramanik, Rajasekaran Ekambaram, Arne Kutzner, Pok-Son Kim, Klaus Heese
Summary: Key factors contributing to tumorigenesis were analyzed through molecular modeling, with withaferin B identified as a lead molecule capable of disrupting the FAM72A-UNG2 interaction, potentially opening up new therapeutic avenues for cancer treatment.
Article
Biochemistry & Molecular Biology
Senthil Renganathan, Sugunakala Subramaniyan, Nivetha Karunanithi, Preethi Vasanthakumar, Arne Kutzner, Pok-Son Kim, Klaus Heese
Summary: This study synthesized silver nanoparticles using Bauhinia tomentosa Linn. flower extract and characterized their properties, as well as found that the biogenic AgNPs exhibit significant antimicrobial and antioxidant activities.
Article
Biochemistry & Molecular Biology
Vijayakumar Maduraimuthu, Jayappriyan Kothilmozhian Ranishree, Raja Mohan Gopalakrishnan, Brabakaran Ayyadurai, Rathinam Raja, Klaus Heese
Summary: This study demonstrates the photoinduced bioreduction of silver nitrate to silver nanoparticles using an aqueous extract of Ulva lactuca. The seaweed extract acts as both a reducing and capping agent, while light serves as a catalyst for biosynthesis. The synthesized nanoparticles exhibit superior photocatalytic activity in degrading hazardous pollutant dyes, indicating their potential for biomedical redox reaction applications.
