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Dr. Susan Shao awarded prestigious 2019 Packard Foundation Fellowship - Oct 19, 2019

Dr. Susan Shao

Assistant Professor Dr. Sichen (Susan) Shao was announced as one of 22 early-career scientists and engineers in the 2019 class of Packard Fellows for Science and Engineering from the David and Lucile Packard Foundation. This $875,000 award will help the Shao Lab study the molecular mechanisms that detect and handle problems at different steps of protein biosynthesis by biochemically rebuilding cellular pathways for mechanistic and structural dissection. Recipients of this prestigious award have gone on to receive numerous accolades, including Nobel Prizes, MacArthur Fellowships, and election to the Nation Academies.

Haigis Lab determines activated T cells need alanine - Sep 27, 2019

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In order to properly respond to invading pathogens, T cells transition from a state of quiescence to a state of activation. This transition is metabolically challenging and to support their growth and functional demands, T cells rely on environmental nutrients. In their recent study published in Cell Reports, the Haigis Lab (in collaboration with the labs of Arlene Sharpe and Josh Rabinowitz) identified extracellular alanine as one of the extracellular nutrients required to support T cell activation. Although alanine is a non-essential amino acid, meaning that it can be synthesized inside the cell via transaminase activity, T cells uniquely rely on the extracellular alanine pool due to low alanine aminotransferase expression. By performing stable isotope tracing, the lab showed that alanine is not catabolized inside the cell but is instead directly shunted into protein synthesis.

Dr. Maofu Liao receives Amgen's 2019 Young Investigator Award - Sep 25, 2019

Dr. Maofu Liao

Dr. Maofu Liao is one of five recipients nationwide of Amgen's 2019 Young Investigator Award, which recognizes rising academic talents whose scientific contributions and commitment to academic excellence greatly impact the field of pharmaceutical research. Along with funding, Dr. Liao will have the opportunity to present a seminar at the annual Young Investigator Award Symposium in October. Congrats, Maofu!

Dr. Randy King nominated for a Donald O’Hara Faculty Prize for Excellence in Teaching - Aug 22, 2019

Dr. Randy King

Congratulations to Randy King, who was nominated for a 2019 Harvard Medical School Donald O’Hara Faculty Prize for Excellence in Teaching. This honor is named in memory of Donald O’Hara, PhD, a beloved teacher of Harvard medical students who served as a leader of the New Pathway Chemistry and Biology of the Cell course and as co-director of the HST course, Human Biochemistry and Metabolic Diseases. The Prize is one of the School's most important commendations for outstanding teaching accomplishments. Congrats to Randy on being nominated and recognized by HMS students as an excellent teacher!

Liao Lab reveals the structure and mechanism of the cation-chloride cotransporter NKCC1 - Aug 13, 2019

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Cation-chloride cotransporters (CCCs) mediate the electroneutral transport of chloride, potassium and/or sodium across the membrane, and play important roles in human physiology and diseases. These transporters are primary targets for some of the most commonly prescribed drugs. As described in a recent paper in Nature, the Liao Lab(in collaboration with Dr. Liang Feng’s lab at Stanford University) determines the cryo-EM structure of the Na-K-Cl cotransporter NKCC1. Structural analyses, functional characterizations and computational studies reveal the ion-translocation pathway, ion-binding sites and key residues for transport activity. These results establish a framework for understanding the physiological functions of CCCs and interpreting disease-related mutations.

Liao Lab determines cryo-EM structure of a large protein organelle for iron sequestration and storage - Aug 13, 2019

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Iron storage proteins are essential for cellular iron homeostasis and redox balance. Ferritin proteins are the major storage units for bioavailable forms of iron. Some organisms lack ferritins, and it is not known how they store iron. In a paper recently published in eLife, the Liao Lab(in collaboration with Dr. Pamela Silver’s lab in the Department of Systems Biology of Harvard Medical School, and Dr. Tobias Giessen at University of Michigan) determines a cryo-EM structure of a 42 nm two-component encapsulin-based iron storage compartment from Quasibacillus thermotolerans. This study reveals the assembly principles of a thermostable T=4 shell topology and its catalytic ferroxidase cargo and show interactions underlying cargo-shell co-assembly. This compartment has an exceptionally large iron storage capacity storing over 23,000 iron atoms, thus revealing a new approach for survival in diverse habitats with limited or fluctuating iron availability via an iron storage system able to store 10 to 20 times more iron than ferritin.

Yuan Lab discovers TAM kinases as mediators of necroptosis - Aug 02, 2019

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Necroptosis is a necrotic programmed cell death mediated by the RIPK1-RIPK3-MLKL signaling cascade downstream of death receptors such as TNFR, Fas and TRAIL. Many neuroinflammatory diseases, including multiple slerosis, ALS, and Alzheimer's disease have been linked to activation of necroptosis. In their study published in Molecular Cell, the Yuan Lab identifies the TAM receptor tyrosine kinase family (Tyro3, Axl, Mer) as novel promoters of necroptosis. TAM kinases regulate the ultimate step in the necroptosis signaling, namely the oligomerization of MLKL, which  results in the formation of a transmembrane pore and cell membrane rupture, driving the necrotic cell death. Both knockout and inhibition of TAM kinases protect mice from TNF-induced systemic inflammatory response syndrome.  This study discovers a novel and unexpected role for the anti-apoptotic, oncogenic, and anti-inflammatory TAM kinases as promoters of the pro-inflammatory necroptosis, shedding light on the biological complexity of regulation of inflammation.

Shi Lab uncovers a new mechanism of gene expression regulation through mRNA modification - Jul 30, 2019

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In order to regulate gene expression, cells utilize diverse molecular mechanisms, one of which is through mRNA modifications. In their study in Molecular Cell, the Shi Lab demonstrates that m6Am is an evolutionarily conserved mRNA modification that marks 5’ ends of mRNAs. In human cells, this mRNA modification is catalyzed only by PCIF1, a nuclear enzyme that binds CTD of RNA PolII. In this study, they further develop a genome-wide mapping methodology, m6Am-Exo-Seq, and generate a global map of this mRNA modification, which reveals a diverse set of methylated mRNAs in melanoma cells. Collaborating with Gygi and Adelman labs at HMS, they further show that m6Am does not alter mRNA transcription or stability, but it negatively impacts cap-dependent translation of methylated mRNAs in vivo and in vitro

Rapoport Lab unveils how the Cdc48/p97 ATPase processes substrates for protein quality control and homeostasis - Jun 27, 2019

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Proteins marked by poly-ubiquitin are degraded by the 26s proteasome. However, if proteins are too well-folded, in complexes, or located within membranes such as in the endoplasmic reticulum or mitochondria, these proteins cannot be directly degraded by the proteasome. To degrade these proteins, a protein called Cdc48 in yeast, named p97 or VCP in metazoans, must first unfold them upstream of the proteasome. Cdc48 is critical for cell viability, and mutations in p97 often lead to various neurodegenerative conditions in humans. In new findings published in Science, the Rapoport Lab used cryo-electron microscopy to understand the mechanism by which Cdc48 can interact with an unfold a wide variety of proteins. Cdc48 recruits the poly-ubiquitin signal, and initiates processing by unfolding a ubiquitin molecule, which it then uses as a handle to pull on, and unfold, attached protein substrates to prepare them for degradation by the proteasome. 

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