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Articles by Michael Yaffe
IDH1-R132H enhances oncolytic HSV-1 therapy by facilitating viral entry and immune activation in glioma
Abstract Oncolytic virotherapy represents a promising yet under-explored approach for precision cancer treatment, particularly when tailored to tumor-specific molecular profiles. Patients with high-grade isocitrate dehydrogenase (IDH) mutant astrocytomas have limited treatment options and poor prognoses. Here, we investigate the therapeutic efficacy of rQNestin34.5 v.2 (CAN-3110), an engineered oncolytic herpes simplex virus 1 (oHSV-1), in IDH1-R132H-mutant diffuse gliomas.
The Fanconi anemia core complex promotes CtIP-dependent end resection to drive homologous recombination at DNA double-strand breaks - Nature Communications
Abstract During the repair of interstrand crosslinks (ICLs) a DNA double-strand break (DSB) is generated. The Fanconi anemia (FA) core complex, which is recruited to ICLs, promotes high-fidelity repair of this DSB by homologous recombination (HR). However, whether the FA core complex also promotes HR at ICL-independent DSBs, for example induced by ionizing irradiation or nucleases, remains controversial.
Signal amplification by cyclic extension enables high-sensitivity single-cell mass cytometry - Nature Biotechnology
Abstract Mass cytometry uses metal-isotope-tagged antibodies to label targets of interest, which enables simultaneous measurements of ~50 proteins or protein modifications in millions of single cells, but its sensitivity is limited.
The intrinsic substrate specificity of the human tyrosine kinome - Nature
Abstract Phosphorylation of proteins on tyrosine (Tyr) residues evolved in metazoan organisms as a mechanism of coordinating tissue growth1. Multicellular eukaryotes typically have more than 50 distinct protein Tyr kinases that catalyse the phosphorylation of thousands of Tyr residues throughout the proteome1,2,3. How a given Tyr kinase can phosphorylate a specific subset of proteins at unique Tyr sites is only partially understood4,5,6,7.
Activation of GPR3-β-arrestin2-PKM2 pathway in Kupffer cells stimulates glycolysis and inhibits obesity and liver pathogenesis - Nature Communications
Abstract Kupffer cells are liver resident macrophages and play critical role in fatty liver disease, yet the underlying mechanisms remain unclear. Here, we show that activation of G-protein coupled receptor 3 (GPR3) in Kupffer cells stimulates glycolysis and protects mice from obesity and fatty liver disease.
USIP’s ‘First in War, First in Peace’ Series
Last Friday, the foreign ministers of Rwanda and the Democratic Republic of the Congo (DRC) met in Washington to sign an agreement to end 30 years of conflict in Africa’s Great Lakes region. The peace deal was accompanied by commitments to build a “regional economic integration framework” and promises of U.S. investment in eastern DRC’s abundant critical mineral reserves, among other commercial agreements.
An atlas of substrate specificities for the human serine/threonine kinome - Nature
Abstract Protein phosphorylation is one of the most widespread post-translational modifications in biology1,2. With advances in mass-spectrometry-based phosphoproteomics, 90,000 sites of serine and threonine phosphorylation have so far been identified, and several thousand have been associated with human diseases and biological processes3,4.
Seeing is great, understanding is better
Michael B. Yaffe is at the Center for Precision Cancer Medicine, Koch Institute for Integrative Cancer Research, and Departments of Biology and Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; and the Divisions of Acute Care Surgery, Trauma and Surgical Critical Care and Surgical Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Monitoring and modeling of lymphocytic leukemia cell bioenergetics reveals decreased ATP synthesis during cell division
Abstract The energetic demands of a cell are believed to increase during mitosis, but the rates of ATP synthesis and consumption during mitosis have not been quantified. Here, we monitor mitochondrial membrane potential of single lymphocytic leukemia cells and demonstrate that mitochondria hyperpolarize from the G2/M transition until the metaphase-anaphase transition. This hyperpolarization was dependent on cyclin-dependent kinase 1 (CDK1) activity.
COVID-19: All the wrong moves in all the wrong places
Abstract In this Editorial, Barrett and Yaffe highlight shortcomings in our collective response to the COVID-19 pandemic and underscore the need for more basic research into this new disease. Christopher D. Barrett Michael B. Yaffe As the world continues to be ravaged by coronavirus disease 2019 (COVID-19), three major systemic failures appear to have coalesced to block progress in disease control, containment, and treatment.
Atlas Drugged
Vasaikar et al. report a comprehensive proteogenomic analysis of 110 colon cancer samples to identify a variety of potential signaling and metabolic targets, neoantigens, and biomarkers. This resource helps expand our understanding of the fundamental pathophysiology of this tumor type, and future mechanistic studies should help guide novel therapeutic strategies for colon cancer treatment.
Why geneticists stole cancer research even though cancer is primarily a signaling disease
Download and print this article for your personal scholarly, research, and educational use. Buy a single issue of Science for just $15 USD.
Predicting the future of signaling for 2018
In this Editorial, the Chief Scientific Editor of Science Signaling predicts some of the emerging areas to watch for advances in signaling research in 2018.
Predicting the future of signaling for 2018
In this Editorial, the Chief Scientific Editor of Science Signaling predicts some of the emerging areas to watch for advances in signaling research in 2018.
Highlight: RNA-binding proteins in cancer
You are currently viewing the abstract.
In Iraq, military defeat of ISIS is only the beginning
The U.S.-backed military operation to rescue Mosul from the grip of ISIS appears to be on the brink of success.
Highlight: Understanding radiation sialadenitis
A nonapoptotic function of caspase-3 underlies the salivary gland complications of radiation therapy of head and neck cancers.
Highlight: A new way to block the development of asthma from dust mites
Highlight: A new way to block the development of asthma from dust mites
Science Signaling Podcast for 14 March 2017: The Cancer Moonshot
This Podcast features a conversation with Science Signaling’s Chief Scientific Editor Michael Yaffe about opportunities for signaling researchers to contribute to the Cancer Moonshot, a federally funded initiative to accelerate cancer research. Administered by the National Cancer Institute (NCI), the goal of the program is to improve the prevention, diagnosis, and treatment of cancer.
Kicking Genomic Profiling to the Curb: How Re-wiring the Phosphoproteome Can Explain Treatment Resistance in Glioma
If you are a current subscriber with Society Membership or an Account Number, claim your access now. Purchase a subscription to gain access to this and all other articles in this journal. Visit ScienceDirect to see if you have access via your institution.
Top 5 Picks For Your Jan. 28 Lineup
TNT’s Thursday doubleheader is complemented by an additional four games to allow for just enough variety to consider GPPs in addition to cash games (which are generally more prudent for the truncated “late” or “express” offerings). Despite an eight-game docket on Wednesday, only the Denver Nuggets and the Atlanta Hawks will be playing the latter half of a back-to-back series and it will also be the fourth game in six nights for each.
Top 5 FanDuel NBA Picks For Your Jan. 27 Lineup
With college football in the books, the NFL winding down and the NHL approaching the All-Star break, the NBA is poised to take center stage in the sports world amid the background noise of ongoing Super Bowl hype.
5 Players Who Can Help Your Jan. 22 FanDuel NBA Lineup
Friday night’s nine-game NBA slate is highlighted by intra-conference matchups that include the Chicago Bulls visiting the Boston Celtics, the Miami Heat traveling north of the border to face the Toronto Raptors and the Oklahoma City Thunder heading to Dallas to meet the Mavericks, who are hopefully closer to full strength this time.
5 Players Who Can Help Your Jan. 20 FanDuel NBA Lineup
After a four-game lull on Tuesday, Wednesday night’s schedule erupts with an 11-game slate that is highlighted by inter-conference matchups such as the Golden State Warriors at the Chicago Bulls, the Detroit Pistons traveling to Space City to face the Houston Rockets and the Atlanta Hawks flying cross-country to face the Portland Trail Blazers in the Rose City.
5 Players Who Can Help Your Jan. 16 FanDuel NBA Lineup
In what has become typical for the NBA weekend schedule, a number of teams in action Saturday night will be playing the latter game of a back-to-back set.
5 Players Who Can Help Your Jan. 15 Lineup
With 18 NBA teams in action, it may seem like a Herculean labor to narrow them down to five building blocks, but fortunately the schedule makers have provided us with a few standout mismatches to help set the stage for this new format.
FanDuel NBA: Best Picks, Lineup For Jan. 13
DeMarcus Cousins, Sacramento Kings ($10,600) vs. New Orleans Pelicans: With 32 (actual) points scored in five of his last six contests, it appears that Cousins has channeled his omnipresent rage into hating the game, at least for now. While his Kings have enjoyed a scheduling break since Saturday, the Pelicans will be on the back end of a two-game set as the third-worst team overall on FanDuel NBA against opposing centers.
FanDuel NBA: Best Picks, Lineup For Jan. 12
Russell Westbrook, Oklahoma City Thunder ($10,900) vs. Minnesota Timberwolves: In what should have been a mismatch on Sunday, the Thunder managed to snatch defeat from the jaws of victory thanks to the Portland Trail Blazers’ fourth-quarter comeback. While it’s probably not much consolation to the crestfallen fans, fantasy owners of the mercurial point guard were rewarded with 60.3 fantasy points for taking a chance that his night wouldn’t be cut short in a blowout.
FanDuel NBA: Best Picks And Lineup For Jan. 8
Russell Westbrook, Oklahoma City Thunder ($10,600) vs. L.A. Lakers: If you have the cap space, Westbrook could be due to go off against a Lakers team that is dead last in the league versus opposing PGs on FanDuel NBA. While the former Bruin has averaged just 28.5 minutes per game in the two previous meetings (both blowouts), the Lakers have shown signs of life lately, winning three straight games before predictably falling to the Golden State Warriors on Tuesday.
FanDuel NBA: Best Picks, Lineup For Jan. 6
Chris Bosh, Miami Heat ($7,900) vs. New York Knicks: After missing an extended portion of last season with blood clots in his lungs, Bosh has re-established himself as one of the top power forwards in the Eastern Conference. He has been particularly dominant at the AmericanAirlines Arena, where he averages 19.6 PPG as opposed to 17.7 PPG elsewhere.
FanDuel NBA: Best Picks And Lineup For Jan. 4
With 10 games on tap, both the Toronto Raptors and the Miami Heat will be playing their second consecutive game and their third in four nights. As discussed in Saturday’s post, we won’t be completely avoiding players from teams in this scenario, but there could be minor downgrades made to the rankings of players from those two squads, and conversely their opponents (the Cleveland Cavaliers and the Indiana Pacers) might be worthy of a slight uptick.
FanDuel NBA: Best Picks, Lineup For Jan. 2
Despite the relatively abbreviated New Year’s Day slate, both the Dallas Mavericks and the Philadelphia 76ers will be playing their second consecutive game and third in four nights. While the fatigue factor may not be as evident as in a squad that is on their fourth game in five nights (for which we’ll reserve the “tired team” designation going forward), it’s something to keep in mind before feeling compelled to go back to the well with the Sixers’ Ish Smith (who’s facing a tough task vs.
FanDuel NBA: Best Picks, Lineup For Dec. 30
Of the 10 teams that played on Tuesday, the Denver Nuggets are the only one that is also in action Wednesday night, and their matchup with the Portland Trail Blazers will be their second consecutive game and their fourth in five nights. Accordingly, all DFS-worthy Portlanders get a huge boost in viability this evening, especially since Denver is a weak defensive team in general. The down side is that the Trail Blazers don’t have many standout options beyond their usual starting guards.
FanDuel NBA: Best Picks And Lineup For Dec. 28
Stephen Curry, Golden State Warriors ($10,900) vs. Sacramento Kings: Curry soldiered on in the Finals rematch against the Cleveland Cavaliers despite a mid-game respite due to his lingering calf injury. Fortunately, the Dubs haven’t been in action since their marquee game on Christmas and the Chef is expected to play tonight. The Warriors’ well-timed schedule break could be bad news for the visiting Kings, who are in the bottom third overall on FanDuel NBA versus opposing point guards.
FanDuel NBA: Best Picks, Lineup For Dec. 26
The schedule makers ran their own version of the “isolation” on Christmas Day, with five consecutive marquee games that had minimal overlap. Despite the relatively light schedule, the Cleveland Cavaliers, Houston Rockets, New Orleans Pelicans and San Antonio Spurs will all be playing their second consecutive game and their third in four days.
FanDuel NBA: Best Picks, Lineup For Dec. 23
The league sends us into the holiday break in grand fashion with a baker’s dozen of games on tap for Wednesday night. Despite the fact that there were only four games scheduled for Tuesday, both the Philadelphia 76ers and the Denver Nuggets have the misfortune of playing their second consecutive game and their third in four nights, so that should favor both the Milwaukee Bucks and the Phoenix Suns, respectively.
FanDuel NBA: Best Picks And Lineup For Dec. 21
Although a nine-game slate might seem a bit daunting, the upcoming holiday break has led to clustered schedules for a number of teams in action that will be playing their second consecutive game and third in four nights.
FanDuel NBA: Best Picks And Lineup For Dec. 18
Carmelo Anthony, New York Knicks ($8,700) vs. Philadelphia 76ers: Whether you love or hate Anthony (or love to hate him), you can’t deny the roll he’s been on lately. At the overripe (by NBA standards) age of 31, Melo has been consistently filling the stat sheet lately, to the tune of 48.5 FPPG over his last three contests.
FanDuel NBA: Best Picks And Lineup For Dec. 16
After a rare Tuesday lull with just four games on the docket, the schedule erupts with a dozen contests for the midweek marathon. As a result, a number of highly-priced studs merit consideration as building blocks, so here is an in-depth look at some of the top choices: Kevin Durant ($10,300) and Russell Westbrook ($10,800), Oklahoma City Thunder vs.
FanDuel NBA: Best Picks And Lineup For Dec. 14
John Wall, Washington Wizards ($9,900) vs. Memphis Grizzlies: Although they are still controlling the pace (23rd out of 30 teams), the Grizz are a far cry from being a defensive juggernaut these days, as they currently sit 25th overall in defensive rating (107.0).
FanDuel NBA: Best Picks, Lineup For Dec. 12
The Peter Principle is a long-standing concept in the business world which postulates that employees will keep getting promoted until they reach a “level of incompetence.” It’s one of those half-truths that is both serious and funny at the same time, and so far it has withstood the test of time since its publication in the late 1960s.
FanDuel NBA: Best Picks And Lineup For Dec. 11
After a four-game lull on Thursday for TNT’s spotlight doubleheader, the schedule has expanded with a vengeance, as there are 11 games on tap for your viewing pleasure. ESPN hosts the twin bill this time, starting with the Miami Heat traveling to Indianapolis to take on the Pacers in a matchup of two foes that have recently reinvented themselves for the better after disappointing 2014-15 campaigns.
FanDuel NBA: Best Picks, Lineup For Dec. 9
A robust 10-game schedule is on tap for Wednesday night, headlined by ESPN’s doubleheader that opens with two Eastern Conference teams that would be in the playoffs if the season ended on Dec. 7; however, the combatants couldn’t be more different from a Fantasy NBA standpoint. The Chicago Bulls are basically a two-headed monster, with Jimmy Butler and Pau Gasol as the only fantasy-worthy players on a regular basis.
FanDuel NBA: Best Picks, Lineup For Dec. 8
There are a number of elite players in action Tuesday night, considering there are only six contests on the docket. What’s even more surprising is that none of them will be on the back end of a two-game set, given that there were 18 teams playing on Monday. For the opening piece we’ll examine the credentials of Tuesday night’s fantasy studs to determine if they are truly worthy of top dollar in consideration for your FanDuel NBA lineup.
FanDuel NBA: Best Picks And Lineup For Dec. 7
The Western Conference has dominated the headlines so far this season, and deservedly so. The Golden State Warriors are still undefeated, the San Antonio Spurs are perfect at home (no one in the East can even make that claim), the Oklahoma Thunder are back to their full complement of players, the Memphis Grizzlies have righted the ship, the Los Angeles Clippers are treading water and the Dallas Mavericks have exceeded expectations after scrambling to field a competitive lineup at the 11th hour.
FanDuel NBA: Best Picks, Lineup For Dec. 5
With college football down to its conference championship games, the NBA has escalated its weekend offerings to a season-high 10-game slate (by Saturday standards), eight of which are relevant for the lion’s share of the DFS tournament offerings. NBA-TV gets the pick of the litter, with LeBron James’ Cleveland Cavaliers testing their mettle against the Miami Heat at the AmericanAirlines Arena.
FanDuel NBA: Best Picks And Lineup For Dec. 4
Friday night’s NBA action is unusually light, with just a half-dozen contests highlighted by an ESPN doubleheader that should be a ratings coup, starting with the NYC area teams facing off and culminating in an inter-conference tilt between the New Orleans Pelicans and the Cleveland Cavaliers, a/k/a “Brow vs.
FanDuel NBA: Best Picks And Lineup For Dec. 3
Thursday is usually a letdown in the NBA schedule for TNT’s spotlight doubleheader, but Thursday night’s six-game slate should allow for good variation among DFS lineups in both cash games and tournament play. The first national game should be an extreme contrast in styles, with the Oklahoma City Thunder visiting Miami to take on the Heat.
FanDuel NBA: Best Buys For Dec. 2
After double-digit games were slated for every Wednesday in November, the schedule got a bit kinder to the fantasy analyst community this evening with “just” nine games on tap. NBA TV’s hostile takeover of national broadcasts concludes with a doubleheader, starting with the New Orleans Pelicans visiting the Space City to take on the Houston Rockets. From a marketing standpoint, game one is really just about Anthony Davis vs. James Harden.
FanDuel NBA: Best Buys For Dec. 1
The lull in the schedule continues with just a half-dozen tilts on tap for Tuesday night. NBA-TV is continuing to own the viewing public’s market share with a doubleheader for their third of four consecutive days of national coverage this week. Is it just me, or is the flagship network broadcasting more of the spotlight games lately? The first game has the disappointing Washington Wizards facing the Cleveland Cavaliers at Quicken Loan Arena.
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