New publication out of the Perrissi Lab “Inhibition of K63 ubiquitination by G-Protein Pathway Suppressor 2 (GPS2) regulates mitochondria-associated translation”

August 21st, 2024in Departmental News, Perissi Lab

The Perissi Lab has recently published in Pharmacological Research a paper titled “Inhibition of K63 ubiquitination by G-Protein Pathway Suppressor 2 (GPS2) regulates mitochondria-associated translation”.

The paper reports the characterization of a novel strategy for regulating mitochondria-associated translation based on the mitochondria retrograde factor GPS2 modulating non-proteolytic ubiquitination of pmitochondria-associated translation factors. Removal of GPS2, either by genomic deletion or via stress-induced translocation to the nucleus, licenses K63 ubiquitination of poly-A binding protein PABPC1 and other factors, favoring translation initiation and promoting the expression of an anti-oxidant stress response program.


Translation of selected nuclear-encoded mitochondrial mRNAs on mitochondria-associated ribosomes provides a unique opportunity for regulating protein translation at single organelle level and thus for coordinating gene expression with mitochondrial health. These findings, together with the previous characterization of nuclear GPS2 as an essential cofactor for the expression of nuclear-encoded mitochondrial genes, reveal that GPS2-mediated inhibition of K63 ubiquitination provides a unifying strategy for modulating the expression of mitochondrial proteins through coordinated transcription and translation events.

The study was led by former postdoctoral fellow Dr. Yuan Gao, in collaboration with the Center for Network Systems Biology and the Lyons Lab.

Welcome New Faculty member – Stefan Isaac, Ph.D.

May 14th, 2024in Departmental News

We are happy to announce that Stefan Isaac, Ph.D., recently accepted our offer to join the department as an Assistant Professor as of July 1, 2024.

 

Dr. Isaac is currently a postdoc with Stirling Churchman at Harvard where he has been carrying out pioneering studies of the mitochondrial genome, a subject that is poorly understood, and whose investigation poses significant experimental challenges. His work is a perfect fit for the genomic and cell biological directions of the department, and he will be able to collaborate with a number of our current faculty members.

Please join us in welcoming Stefan!

New publication from the Cifuentes Lab uncovers a cross-talk between microRNA and chromatin regulators

May 14th, 2024in Departmental News, Seminars

The Cifuentes Lab has recently published a paper in Nature Communications (rdcu.be/dHdub) that sheds light on the intricate mechanisms governing the differentiation of stem and progenitor cells during erythropoiesis. In their study, they delved into the post-transcriptional regulatory layer orchestrated by miR-144 and discovered its pivotal role in chromatin condensation during erythrocyte maturation.

Using genetic and genomic approaches in zebrafish embryos and human iPSC cells, they unveil a regulatory axis conserved across vertebrates involving miR-144 and Hmgn2 and demonstrated that it is essential for terminal erythrocyte maturation.

The study also offers insights into how microRNAs can expand their regulatory network. The loss of miR-144 not only affects its direct targets but also leads to dysregulation of additional non-target mRNAs thanks to the downregulation of a chromatin regulator, Hmgn2. These results emphasize the complexity of miRNA-mediated regulatory networks in cellular differentiation and development.

Overall, these findings will contribute to a deeper understanding of the intricate regulatory networks underlying cell differentiation.

This work was spearheaded by Dmitry Kretov (Instructor) in collaboration with the Vanuystel lab and the Murphy lab at the CReM and the bioinformatic support of Leighton Folkes and Simon Moxon (University of East Anglia, UK).

Two new publications from the Garcia-Marcos Lab

March 27th, 2024in Departmental News, MGM lab

In a first publication, the Garcia-Marcos Lab has recently published the development and implementation of a suite of G protein biosensors broadly applicable to detect GPCR activity in scalable assay formats and in physiologically relevant systems like primary cells. By directly measuring endogenous GPCR activity, these biosensors, named ONE-GO, reveal that responses are frequently dependent on the cell context or state. This resource article has been published in the journal Cell  (https://www.sciencedirect.com/science/article/pii/S0092867424000655?via%3Dihub) and all related plasmid reagents are deposited in Addgene (https://www.addgene.org/kits/garcia-marcos-one-go-biosensors/). The work in this paper was led by current PhD student Remi Jnaicot and former postdoc Marcin Maziarz, and includes collaborations with the Layne Lab in our Department and the Wu lab at Stanford.

In a second paper, Mikel has reviewed a lot of the research related to his lab's work on atypical mechanisms of signaling over the last 15 years.G proteins are molecular switches that relay signals from G protein-coupled receptors across the cell membrane. While it is generally assumed that G proteins, molecular switches that trasnduce signals, are activated exclusively by G protein-coupled receptors (GPCRs), this review summarizes the mounting evidence showing that G proteins can signal via a class of G protein regulator proteins that contain a Gα-binding-and-activating (GBA) motif. The mechanisms and structural basis for this GPCR-independent mechanism of G protein signaling are presented, as well as a description of strategies to manipulate GBA-G protein coupling for research purposes or the potential development of therapeutics. This paper has been published as a commissioned review in the Journal of Biological Chemistry (https://www.sciencedirect.com/science/article/pii/S0021925824001327?via%3Dihub).

Congratulations to David A. Harris, M.D.,Ph.D. on being awarded The Edgar Minas Housepian, MD, Professorship

Congratultions to David A. Harris on being one of 5 recipients of the Edward Avedisian Professorships. 

 

The Edgar Minas Housepian, MD, Professorship went to David A. Harris, chair of biochemistry andcell biology since 2009. He studies molecular and cellular mechanisms underlying human neurodegenerative diseases. His work on infectious prion diseases like mad cow disease, where brain proteins fold and can result in neurodegenerative effects, has helped research into other neurodegenerative diseases, like Alzheimer’s, Parkinson’s, and Huntington’s.

“What I want to highlight here is the incredible foresight to use that endowment ($25 million of the Avedisian endowment is dedicated to research and teaching) to support basic research, which is…always at the root of great medical discoveries,” said Harris. “I am honored to be associated with a legacy that values the pursuit of knowledge and scientific excellence.”

Housepian was a renowned neurosurgeon at New York-Presbyterian Hospital and professor of neurology at Columbia University’s medical school, where he taught for 44 years.

“He was a very creative person with a long-range vision,” said his daughter, Jean Housepian. Even with a career that began in labs, then surgery, education remained his key concern, and in his retirement years, he remained an advocate for international educational affiliations for medical students.

See the whole article here.

Mikel Garcia-Marcos elected Chair of Division of National Scientific Society

March 1st, 2024in Departmental News, MGM lab

Mikel Garcia-Marcos has been elected as Chair of the Division of Molecular Pharmacology of the American Cancer Society of Pharmacology and Experimental Therapeutics (ASPET).

He will serve a 1-year term as Chair-Elect followed by a 1-year term as Chair. In this role, he will oversee the activities of the Executive Committee involving planning of the Society's Annual Meeting, financially supporting external scientific meetings, selection of scientific achievement awardees, and organizing other activities like online webinars and workshops.

The American Society for Pharmacology and Experimental Therapeutics (ASPET) is a 4,000 member scientific society whose members conduct basic and clinical pharmacological research and work for academia, government, large pharmaceutical companies, small biotech companies, and non-profit organizations. ASPET is a global pharmacology community that advances the science of drugs and therapeutics to accelerate the discovery of cures for disease.

Congratulations to Daniel Cifuentes on his recent promotion to Associate Professor of Biochemistry & Cell Biology!

February 14th, 2024in Departmental News

Congratulations to Daniel Cifuentes on his recent promotion to Associate Professor of Biochemistry & Cell Biology!

Research goals in the Cifuentes laboratory aim to understand the molecular mechanisms of RNA regulation. In particular, they focus on the study of RNA-binding proteins, microRNAs, and RNA modifications to uncover their impact on small RNA biogenesis and mRNA post-transcriptional regulation.