Hashim M. Al-Hashimi, PhD

Al-Hashimi is interested in developing a deep, quantitative, and predictive understanding of cellular processes based on the fundamental behaviors of nucleic acids and their interactions with protein binding partners.  Over the past two decades, Al-Hashimi and his trainees developed approaches combining NMR spectroscopy, computational modeling, optical melting experiments, and chemical probing to determine 3D dynamic ensembles of RNA and DNA molecules at atomic resolution.  Using dynamic ensembles of nucleic acids, the Al-Hashimi group has developed quantitative and predictive models for several fundamental biological processes, including DNA replication fidelity, Tat-dependent HIV-1 transcriptional activation, RNA folding, and the impact of post-transcriptional modifications such as m6A and Nm on translation, splicing, and RNA-protein interactions.  These studies have reshaped structural biology, revealing dynamic ensembles as the fundamental behavior of biomolecules needed to understand and predict cellular activity quantitatively.

The Al-Hashimi lab is currently using dynamic ensembles to reconstitute the folding and cellular activities of viral and other non-coding RNAs, to determine the role of DNA structural dynamics in shaping the probabilities of mutagenesis and cancer, and to rationally design inhibitors targeting viral RNA regulatory elements in HIV-1 and SARS-CoV-2 as well as non-coding RNAs involved in cancer.  Efforts include developing and applying high throughput sequencing-based approaches to map DNA structural dynamics genome-wide, developing high throughput assays for quantitatively measuring the activity of various steps in the HIV-1 lifecycle, and determining an atlas of dynamic ensembles for all nucleic acid building block motifs.  A more recent area includes efforts to digitize biochemistry by describing biomolecules in terms of finite-state-computing machines and applying complexity theory to classifying biochemical reactions.

As a mentor, Al-Hashimi is strongly committed to creating a welcoming, enriching, and supportive environment for all his trainees and effectively preparing them for careers in science.  To date, he has trained over thirty-five graduate students and postdoctoral fellows with backgrounds in biochemistry, cell biology, chemistry, computer science, physics, and mathematics.  His alumni include heads of laboratories at universities in the US, France, Sweden, India, and China and scientists at many biotech companies, large pharmaceutical firms, and management consulting firms.  Over 30 undergraduates have also worked in the Al-Hashimi laboratory.

Al-Hashimi Lab: https://www.biochem.cuimc.columbia.edu/research/research-labs/al-hashimi...