Dr. Denise O.

A very special first post on Bluesky: I’m excited to share that I’ll be starting my lab at Penn State this coming January in the Dept of Biochemistry & Molecular Biology! I’ll be hiring at all levels soon. Check out updates, thoughts, and positions on the lab account: @hanna-lab.bsky.social

Opinion | Science Suffers With Trump’s Funding Freeze America’s scientific enterprise demands reliable stewardship, not destabilizing political intervention.

My father-in-law, Jack Strominger, and I wrote a letter to the @wsj.com editor about the current threats to science due to Trump's funding freeze. Please repost! www.wsj.com/opinion/scie...

What a delightful visit to Penn State, hosted by @cdokafor.bsky.social! 🙌 We cooked up a new collab, had a fun new PI dinner with @erdavenport.bsky.social, AND I managed to reclaim some joy by talking chromatin & mentoring with the great folks in BMB. (Forever grateful for our Emory IRACDA fam!)

Today is the 5th anniversary of the lab! Thankful for the home I've found at Penn State and the people I've found it with. Happy new year!

we extended our simulations to the full length heterodimer complex between FXR and RXR (retinoid X receptor alpha). We revealed a variety of underappreciated roles for the FXR hinge in the context of the dimer, including in DNA binding, interdomain allostery and dimer flexibility

6. Simulations Reveal Unique Roles for the FXR Hinge in the FXR–RXR Nuclear Receptor Heterodimer (Nov 2024) in the 2024 Rising Stars in Biological, Medicinal, and Pharmaceutical Chemistry edition of ACS Bio & Med Chem Au.

t.co/vj7z16cePG

In this work, we used simulations and experiments on full length farnesoid X receptor (FXR) to show for the first time that ligands selectively mediate contact betwen the DNA and ligand binding domains. We showed that the interdomain hinge plays an active role in this process

5. Nuclear Receptor Interdomain Communication is Mediated by the Hinge with Ligand Specificity (Nov 2024) in J. Mol. Biol.

t.co/UMfRvr1bBG

In this work, we performed extensive analysis on 27 nuclear receptor complexes, aimed at learning how simulation lengths and number of replicas affect results obtained from MD studies. This work provides a benchmark for researchers studying similar research questions/size systems

4. Impact of Replicas and Simulation Length on In Silico Behaviors of a Protein Domain (October 2024) in ChemPhysChem as part of the Physical Chemistry Talents collection.
t.co/m6qGO4vPEO

We used MD simulations to show that PR evolved a distinct mechanism of activation from other steroid hormone receptors. However it maintains vestiges of this ancient mechanism, allowing it to be weakly activated by certain hydroxylated steroidal ligands.

3. Illuminating ligand-induced dynamics in nuclear receptors through MD simulations (June 2024) - a review article published in Biochim Biophys Acta Gene Regul Mech.

t.co/IVSXwVtUog

We used MD simulations to show that PR evolved a distinct mechanism of activation from other steroid hormone receptors. However it maintains vestiges of this ancient mechanism, allowing it to be weakly activated by certain hydroxylated steroidal ligands. #rscchembio

2. Ancient and modern mechanisms compete in progesterone receptor activation (Feb 2024). published in
RSC Chem. Bio. as part of the 2023 RSC Chemical Biology Emerging Investigators themed edition.

t.co/zQNbH95whN

We study the transition betweeen active and inactive conformations of the PR ligand binding domain. We show that active and inactive states represent global and local minima respectively, the transition between them is ligand modulated, and occurs on millisecpmd timescales. #jcp

1. How nuclear receptors transition between active and inactive forms: An energetic perspective (Jan 2024). Published in J. Chem Phys as part of the 2024 JCP Emerging Investigators Special Collection
t.co/4dEiD6vNKs

we study the origin of potency in agonists of the farnesoid X receptor. We show that bile acids induce dynamic coupling between helices 5 and 7 of the ligand binding domain. A modification on the bile acid scaffold further strengthens this coupling, explaining its higher efficacy

7. Enhanced dynamic coupling in a nuclear receptor underlies ligand activity
t.co/CJmX1WQToW

I am excited to share our work in
J. Mol. Biol. which is our 7th publication on #nuclearreceptors for the 2024 calendar year! Please read on for a summary of all 7 publications from our lab this year, as well as links to the papers.