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<p>As life expectancy increases, age-related diseases are becoming more prevalent. While these conditions are traditionally studied in isolation, mounting evidence points to shared, systemic mechanisms underlying these conditions. Our research highlights the vasculature as &nbsp;a key player in organ homeostasis and repair, and a system shared across all organs—making its dysfunction potential driver of age-related pathologies.</p><p>We demonstrate that manipulating <strong>VEGF signaling</strong> to counteract age-related microvascular rarefaction promotes <strong>comprehensive geroprotection</strong>, preserving organ function and delaying disease onset. Our findings also reveal a link between vascular rarefaction and altered RNA splicing. While hypoxia-driven and age-related changes in alternative RNA splicing have been studied independently, we propose a unifying mechanism that links the two. To explore this further, we also employ patient-derived organoids, which retain their biological age in culture, providing a robust in vitro platform to test anti-aging interventions.</p><p>Our findings support a <strong>vascular theory of aging</strong>, identifying vascular health as a promising target to mitigate age-related diseases and promote healthier aging.</p>

<p>Over the past few decades, immunotherapy has revolutionized cancer treatment with great success in treating cancer patients and preventing tumor recurrence after surgery. Harnessing the immune system to fight cancer largely relies on the ability of T lymphocytes to distinguish&nbsp;between “self” and “non-self” to specifically identify and eliminate malignant cells.&nbsp;This is achieved through the recognition of neoantigens, tumor-specific proteins resulting from genetic mutations.</p><p>The Samuels’ lab is exploring the immune-tumor interactions, with specific focus on the mechanisms underlying cancer-cell recognition, and developing novel strategies to increase antitumor immune responses.</p><p>In this talk, I will present results from our recent studies investigating the link between mRNA mistranslation in cancer cells and immunological tumor control.</p>

<p>N2 fixation is the primary pathway by which bioavailable nitrogen is added to the</p><p>oceans. However, the drivers of N2 fixation on orbital timescales are uncertain. We</p><p>present high-resolution foraminifera-bound (FB) δ15N records from the Western</p><p>and Eastern tropical Atlantic Ocean (WTA and ETA respectively) throughout the</p><p>late Pliocene (~3.60 to ~1.97 Ma), where WTA ODP Site 999 represents N2</p><p>fixation changes and EEA ODP Site 662 represents changes in pycnocline δ15N.</p><p>Our results show that, compared to the past 160 ka, N2 fixation in the WTA was</p><p>significantly lower throughout the late Pliocene as reflected by an average of ~2 ‰</p><p>higher FB-δ15N values. A possible explanation to the higher Pliocene FB-δ15N in</p><p>the WTA could be lower rates of global denitrification that were balanced by lower</p><p>global N2 fixation levels. We suggest that this reduced N2 fixation was due to</p><p>decreased excess P in the pycnocline/subsurface ocean, driven by lower global</p><p>water column denitrification. This finding implies a coupling between decreased</p><p>water column denitrification and reduced level N2 fixation rates under warmer</p><p>climates.</p><p>On orbital timescales, our N2 fixation record display obliquity-paced cycles that</p><p>progressively intensified after the Northern Hemisphere glaciation intensification ~</p><p>2.8 Ma, and the onset of equatorial upwelling pulses documented during glacial</p><p>periods in the EEA (ODP Site 662; [1]). The observed changes in N2 fixation of the</p><p>last 160 ka were previously explained by precession-paced upwelling in the EEA</p><p>that imported excess P into the oligotrophic WTA [2]. However, precessional</p><p>cyclicity is not dominant in the Pliocene FB- δ15N, which calls for other candidates</p><p>to explain the variations after 2.8 Ma. The best explanation is a response to sealevel</p><p>paced sedimentary denitrification. Glacial lower sea levels exposed</p><p>continental shelves, reducing regional benthic denitrification and inhibiting the</p><p>supply of excess P, thereby limiting N2 fixation in the WTA, whereas interglacial</p><p>submerged shelves increased excess P availability.</p>

TBD

<p>Post-translational modifications of histones play a central role in regulating all cellular processes requiring access to DNA. Monoubiquitinated histone H2B-K120 is a hallmark of actively transcribed genes that plays multiple roles in activating transcription, while monoubiquitinated histone H2A-K119 is abundant in heterochromatin, which is transcriptionally silent. Our structural studies have revealed how histone H2B is specifically ubiquitinated and deubiquitinated, and ubiquitinated H2B stimulates histone methylation. We have also shown how ubiquitin can regulate access to the nucleosome acidic patch, a hotspot for interactions with other chromatin-modifying enzymes. I will also discuss recent studies of a histone kinase that has an unusual mode of binding nucleosomes.</p>