Exploring excited-state proton transfer reactions in isothiazologuanosine, an isofunctional fluorescent analogue of guanosine.

To fully exploit the potential of isothiazologuanosine (G), an isomorphic and isofunctional fluorescent analogue of guanosine, as a probe for DNA and RNA, we characterized its photophysics and in particular its excited-state reactions over a wide pH range (-0.6 to 12) and time scale (100 fs-100 ns) by combining transient absorption and time-correlated single photon counting measurements with quantum mechanical calculations. At acidic pH, the dominant ground-state species G-H1-H3, where the N atoms in positions 1 and 3 are protonated, rapidly converts to the more stable tautomer G-H1-H7 in its excited state.

GCAD: a Computational Framework for Mammalian Genetic Program Computer-Aided Design.

Genetic programs can direct living systems to perform diverse, pre-specified functions. As the library of parts available for building such programs continues to expand, computation-guided design is increasingly helpful and necessary. Yet key gaps exist for designing programs for use in mammalian cells in particular.

Identifying Drug Combination Strategies for Fusion Positive Leukemia.

Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions (MLN-TK) are a class of fusion protein-driven, poor prognosis leukemias. Leukemias harboring FGFR1 fusions have previously been referred to as 8p11.2 myeloproliferative syndrome (EMS) or stem cell leukemia/lymphoma (SCLL) and are currently referred to as Myeloid/lymphoid neoplasms with FGFR1 rearrangement based on the most recent WHO classification system.

Conversion of natural cytokine receptors into orthogonal synthetic biosensors.

Synthetic receptors enable bioengineers to build cell-based therapies that perform therapeutic functions in a targeted or conditional fashion to enhance specificity and efficacy. Although many synthetic receptors exist, it remains challenging to generate new receptors that sense soluble cues and relay that detection through orthogonal mechanisms independent of native pathways. Here we co-opt natural cytokine receptor ectodomains into modular extracellular sensor architecture (MESA) receptors to form natural ectodomain (NatE) MESA receptors.

The impact of social determinants of health on outcomes of brexucabtagene autoleucel in adults with relapsed/refractory B-cell acute lymphoblastic leukemia.

Brexucabtagene autoleucel (brexu-cel) is a chimeric antigen receptor T (CAR T) cell therapy approved for adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). We studied the impact of social determinants of health (SDoH) on outcomes of adults with B-ALL receiving brexu-cel. This retrospective analysis included adults (≥18 years) with R/R B-ALL treated with brexu-cel between 2021 and 2023.