Research Projects
DNA Self-Assembly by Protamines In Vitro and In Vivo.
In nature, DNA is tightly packed through complex interactions with proteins such as histones in eukaryotic nuclei or protamines in sperm cells. The degree of compaction is immense: nearly 2 meters of DNA are condensed into a human cell nucleus just 10 microns wide. In sperm cells, this compaction is even more extreme, with about 1 meter of DNA packed into a nucleus roughly one-tenth the size of a somatic cell nucleus. Our research explores the fundamental biophysical mechanisms behind DNA condensation, particularly focusing on how cations mediate DNA-DNA interactions. By integrating advanced techniques such as x-ray scattering and osmotic stress, we aim to connect in vitro models to the highly specialized packaging observed in mammalian sperm. Ultimately, we seek to understand how protamine function and dysfunction affect DNA packaging, leading to chromatin mispackaging, DNA damage, and its broader implications for fertility, aging, and disease. |
Synthesis and Development of New Polymers for Optimized Delivery of Nucleic Acids
The design of gene delivery polymers poses a complex challenge: these materials must protect delicate nucleic acids (NA) from degradation by nucleases while also facilitating efficient cellular uptake and timely cargo release. Our research addresses this balancing act by synthesizing and characterizing novel polymers tailored for nucleic acid delivery. We focus on elucidating the mechanisms behind polymer-NA interactions, investigating how polymer/NA complexes (polyplexes) form and behave in biological environments. By exploring how these structures influence intracellular trafficking and gene delivery efficiency, we aim to inform the next generation of gene delivery technologies with enhanced therapeutic potential. This work not only pushes the boundaries of polymer science but also opens new doors for treating genetic diseases and cancers. |
Developing Hydrogels for Mitochondrial Transplantation
Mitochondrial transplantation has emerged as an exciting frontier in regenerative medicine, with the potential to restore cellular energy production in damaged tissues. However, key challenges remain, particularly in ensuring the precise delivery and long-term survival of transplanted mitochondria. In collaboration with engineers and the Spinal Cord and Brain Injury Research Center (SCoBIRC), we are developing innovative thermo-responsive hydrogels that encapsulate mitochondria for controlled, sustained release into injured tissues. These hydrogels not only provide a protective environment for the mitochondria but also enhance their viability, significantly improving bioenergetic recovery and functional outcomes in spinal cord injury (SCI) models. This work has broad implications for developing new therapeutic strategies for a wide range of conditions involving mitochondrial dysfunction. |
Nanoparticle Transport in Complex Media
Delivering gene therapy constructs to target cells requires overcoming numerous biological barriers, including the extracellular matrix (ECM)—a dense network of proteins and polysaccharides—as well as mucus layers and biofilms that can trap particles or bacteria. These complex environments present unique challenges, with a variety of specific and nonspecific interactions, including electrostatic forces and chemical binding, complicating diffusion and transport. Our group tackles these challenges by studying the fundamental transport mechanisms of gene therapy constructs in these crowded biological systems. Using cutting-edge techniques such as fluorescence correlation spectroscopy (FCS), we are unraveling how nanoparticles and other therapeutic agents interact with biological barriers. By improving our understanding of these processes, we aim to optimize the delivery of nanoconstructs, enhancing the efficacy of treatments for a range of diseases. |