Dr. Hudalla Selected To Receive UF Term Professorship

Congratulations to Dr. Hudalla on being selected to receive a three-year University of Florida Term Professorship.

This recognition is for excellence in teaching, research and service recommended by their college deans based on nominations from their department chairs and reviewed by the College Honors and Awards Committee.

Hudalla’s research creates functional biomaterials for therapeutic or diagnostic applications via molecular self-assembly. The Hudalla laboratory develops synthetic peptides that can assemble into a desired nano-scale architecture, and then uses these peptides as “tags” to organize biologically active molecules into functional nanomaterials. For example, their work has led to glycosylated nanofibers that inhibit the immunomodulatory activity of galectins, a family of carbohydrate-binding proteins. In another project, they combine enzymes and carbohydrate-binding proteins into catalytic nanomedicines that are anchored to tissues at an injection site via binding to extracellular carbohydrates. Hudalla’s long-term goals are to create biomaterials that can modulate immune responses for the treatment of autoimmune diseases and aberrant inflammation.

 

Hudalla and Keselowsky Collaboration Published in Nature Communications

Congratulations to Dr. Gregory A. Hudalla, assistant professor, Dr. Benjamin G. Keselowsky, professor, and their team on their manuscript titled, “Locally Anchoring Enzymes to Tissues via Extracellular Glycan Recognition,” that has been published in Nature Communications.
 
Their collaborative research seeks to address the unmet challenge of installing enzymes within specific tissues to alter local biochemistry while avoiding widespread distribution that leads to off-target changes in organism biochemistry.
 
Despite more than 50 years of active research, the use of enzymes in medicine remains limited by safety issues resulting from unfavorable pharmacokinetics and pharmacodynamics. This is primarily because a small amount of enzyme can quickly convert a very large quantity of substrate into product.

To achieve this objective, they engineer enzymes to bind to extracellular carbohydrates. The key advances with their strategy are: (1) enzyme residence time can be tuned by varying the number of carbohydrate-binding anchoring units; (2) by targeting common carbohydrates, it is applicable to any tissue site that can be accessed via minimally-invasive injection or during surgical procedures; and (3) it leverages conserved carbohydrates, making it translatable across humans and various animal species.
 
The impact of this research is to advance enzymes as therapeutics while also fostering new ideas in protein engineering. The ability to engineer local biochemistry by introducing specific enzymes at the right time and place within the body would afford new opportunities to treat diseases such as cancer, metabolic disorders, and autoimmunity, fight infection, enhance wound healing, and promote tissue regeneration. To realize this potential though, approaches are needed to transiently install enzymes within specific tissues to engineer local biochemistry while avoiding widespread distribution that results in off-target reactions throughout the organism.
 
Nature Communications is a peer-reviewed open access scientific journal published by the Nature Publishing Group. It covers the natural sciences, including physics, chemistry, earth sciences and biology.

For more information see the Behind the Paper story published on the Nature Research Bioengineering Community blog.

Hudalla Recieves 2018 Early Career Award

October 25, 2018

Congratulations to assistant professor, Dr. Gregory Hudalla, who received the 2018 Early Career Award from the University of Wisconsin-Madison College of Engineering.

Each year, the University of Wisconsin-Madison College of Engineering recognizes outstanding alumni during Engineers’ Day—a celebration of engineers.

Read more from his interview with the UW-Madison COE here.

Dr. Hudalla Awarded NIBIB Trailblazer R21 Award

Dr. Gregory A. Hudalla, assistant professor & J. Crayton Pruitt Family Term Fellow, was recently awarded a National Institute of Biomedical Imaging and Bioengineering (NIBIB) Trailblazer R21 Award for his grant entitled, “Supramolecular hydrogels for localized delivery of immunomodulatory enzymes.”

The proposed project aims to develop biomaterials with integrated immunomodulatory enzymes as a new treatment modality for inflammatory diseases. States of chronic inflammation resulting from aberrant immune system recognition of self as non-self are a significant clinical and financial burden because they are often incurable, and are typically managed by administering costly biologic drugs that can render patients immunodeficient or immunocompromised. With this award, the proposed research program will develop locally administered biomaterials that can recapitulate natural mechanisms to locally resolve inflammation via enzymes that catalyze the conversion of immunostimulatory signals to immunosuppressive signals.

The Trailblazer R21 Award is an opportunity for new and early stage investigators to pursue research programs of high interest to the NIBIB at the interface of the life sciences with engineering and the physical sciences. A Trailblazer project may be exploratory, developmental, proof of concept, or high risk-high impact, and may be technology design-directed, discovery-driven, or hypothesis-driven.

Hall, Hudalla, and Paravstu Receive $1 Million NSF RAISE Grant

Dr. Gregory A. Hudalla, assistant professor and J. Crayton Pruitt Family Term Fellow, and collaborators were recently awarded a $1 million NSF RAISE grant entitled, “RAISE: Design of co-assembling peptides as recombinant protein fusion tags for integrating enzymes into supramolecular hydrogels.” 

The NSF Research Advanced by Interdisciplinary Science and Engineering (RAISE) program supports lines of research that promise transformational advances through prospective discoveries that reside at the interfaces of disciplinary boundaries and thus lie outside the scope of a single NSF program. This RAISE project is jointly funded by the Biological and Environmental Interactions of Nanoscale Materials program in CBET Division in the Engineering Directorate, the Molecular Biophysics Program in the Division of Molecular and Cellular Biosciences in the Biological Sciences Directorate, and the Office of Integrative Activities. 
 
The multi-institutional team of Dr. Carol Hall, Camille Dreyfus Distinguished Professor at NC State University, Dr. Anant Paravastu, associate professor at Georgia Tech, and Dr. Hudalla, combine their expertise in computational modeling, biophysical characterization, and nuclear magnetic resonance to study peptide assembly into supramolecular (‘beyond the molecule’) structures. This RAISE award supports their on-going efforts to advance understanding of “peptide co-assembly” — the formation of a single supramolecular structure via interactions between two unique peptide molecules — as well as to use co-assembling peptides attached to proteins as a general strategy to create functional supramolecular biomaterials. The goals of this project are to establish a computational-experimental framework to uncover molecular-level design rules necessary to predict peptide co-assembly, and then to use these rules to develop novel enzyme-functionalized supramolecular biomaterials. This approach is anticipated to provide an extraordinary near-term improvement over the current state-of-the-art in enzyme immobilization methods, while also having a broader transformative impact on designing novel functional biomaterials for medical and technological applications.

http://bme.ufl.edu/node/2029

Dr. Hudalla and Dr. Keselowsky Awarded $2.1 million NIH Grant to Manage Inflammation in Periodontal Disease

Periodontal disease refers to the inflammatory processes that occur in the tissues surrounding the teeth in response to bacterial accumulations, or dental plaque, on the teeth. The chronic and progressive inflammation of the gums leads to bone destruction and loss of tissue attachment to the teeth.

The aim of this research is to develop a new approach of administering enzymes to locally shut down the inflammation associated with periodontal infection. Drs. Keselowsky and Hudalla have fused two proteins together to endow an enzyme which breaks down tryptophan and produces molecules called kynurenines, a powerful anti-inflammatory combination, with prolonged tissue retention capability using proteins that bind carbohydrates found in tissues.

http://bme.ufl.edu/node/2032

Dr. Hudalla Receives the new Pruitt Family Endowed Faculty Fellowship

December 08, 2016

The J. Crayton Pruitt Family Department of Biomedical Engineering is proud to announce the awardees of the Pruitt Family Endowed Faculty Fellowships to recognize talented junior faculty!

Congratulations to:

  • Dr. Kyle D. Allen, assistant professor and associate chair of undergraduate studies
  • Dr. Aysegul Gunduz, assistant professor
  • Dr. Gregory A. Hudalla, assistant professor

The Pruitt Family Endowed Faculty Fellowships was established this year through the generosity of Dr. J. Crayton Pruitt, Sr. Allen, Gunduz and Hudalla were awarded the fellowships during the department’s 5th Annual Pruitt Research Day. We hold Pruitt Research Day near the birth date Dr. J. Crayton Pruitt Sr. whose vision and generosity helped found the department.

Criteria for the selection was excellence in teaching and research, as evidenced by strong teaching evaluations in required as well as elective BME courses, research mentorship of BME PhD and BS students, prestigious external research recognitions including major publications, awards and/or grants. Appointment is for a one-time, three-year term.

Congratulations to Drs. Kyle D. Allen, Aysegul Gunduz and Gregory A. Hudalla!

http://bme.ufl.edu/node/1893

Dr. Hudalla named 2016 Young Innovator by the CMBE

August 24, 2016

Dr. Gregory A. Hudalla, assistant professor in the J. Crayton Pruitt Family Department of Biomedical Engineering, is named a 2016 Young Innovator by the journal Cellular and Molecular Bioengineering (CMBE).

Cellular and Molecular Bioengineering, an official journal of the Biomedical Engineering Society (BMES), publishes research that advances the study and control of mechanical, chemical, and electrical processes of the cell. Each year, the editors of CMBE dedicate the Young Innovators special issue to highlighting the work of assistant professors conducting innovative bioengineering research at the molecular, cellular, and multi-cellular level.

Hudalla’s research focuses on developing new methods to fabricate biomaterials with modular therapeutic or diagnostic capabilities via self-assembly of functional biomolecules, such as proteins and carbohydrates, into precise nano-scale architectures. In the 2016 CMBE Young Investigator issue, Hudalla and co-authors report on their work creating a pair of oppositely-charged synthetic peptides, referred to as “CATCH” (Co-assembly tags based on charge complementarity), to install folded proteins into self-assembling biomaterials.  The two CATCH peptides were designed to spontaneously associate into elongated nano-scale fibers when combined in water, yet resist assembly with self-due to like-charge repulsion. This charge-controlled assembly enables efficient microbial production of “fusion proteins” consisting of a CATCH peptide linked to a protein having desirable functional property, such as fluorescence. In turn, CATCH fusion proteins can assemble into functional biomaterials, such as particles and gels, by simply mixing them with the charge-complementary CATCH peptide in water. Hudalla and co-authors envision that this platform will be broadly useful for creating functional biomaterials with interchangeable integrated folded protein components for various biomedical and biotechnological applications.

As a 2016 CMBE Young Innovator, Hudalla will present his research at the 2016 Annual Biomedical Engineering Society Meeting in Minneapolis, Minnesota, on October 7 in a special two-part platform session of the Bioengineering track.

https://www.bme.ufl.edu/node/1835

Antonietta’s review paper featured on front cover of J. Materials Chemistry B

Congratulations to Antonietta Restuccia, Maggie Fettis and Dr. Gregory Hudalla for co-authoring a review article “Glycomaterials for immunomodulation, immunotherapy and infection prophylaxis,” which was featured on the front cover of the ninth issue of Journal of Materials Chemistry B.

Antonietta Restuccia and Margaret M. Fettis, both UF BME Ph.D. students in Dr. Hudalla’s lab, co-authored the review article which begins by highlighting the integral role of carbohydrates in innate and adaptive immunity, and provides a detailed survey of emerging synthetic materials modified with carbohydrates (‘glycomaterials’) to harness their biological activity.

Carbohydrates present on the surface of cells or within the extracellular matrix can bind to various soluble and membrane proteins, and these highly specific molecular interactions are important regulators of various immune-related processes, such as inflammation, adaptive memory and tolerance. The article surveys major on-going research efforts to develop glycomaterials that can engage the immune system to prevent or treat diseases. For instance, emphasis is placed on glycomaterials that can inhibit T cell apoptosis, establish antigen-specific tolerance, suppress inflammation, and inhibit viral entry into host cells by modulating the biological activity of carbohydrate-binding proteins. Also, this report surveys recent successes in using glycomaterials as both vaccines to raise adaptive immunity against tumor-associated carbohydrate antigens, and as diagnostic tools to study anti-carbohydrate immunity.

Throughout the article, challenges associated with glycomaterials design and efficacy are discussed, which include the complexity of carbohydrate synthesis, achieving selective targeting of particular carbohydrate-binding proteins, poor carbohydrate stability due to enzymatic degradation, and low protein-carbohydrate binding affinities. They emphasize key features that prove to be critical when engineering glycomaterials, for example, multivalent carbohydrate display, carbohydrate valency, ligand flexibility and availability.

The Journal of Materials Chemistry B is part of the Royal Society of Chemistry Publishing, focusing on the materials field. The journal is interdisciplinary, publishing work of international significance on all aspects of materials chemistry related to biology and medicine.

https://www.bme.ufl.edu/node/1791

Maggie & Wei’s research featured in J. Materials Chemistry B Hot Papers

February 21, 2016

Congratulations to Maggie Fettis, Yaohua Wei, Dr. Gregory Hudalla, et al.  for co-authoring their article “Microgels with tunable affinity-controlled protein release via desolvation of self-assembled peptide nanofibers,”  which was featured in the 2016 Journal of Materials Chemistry B Hot Papers.

With a growing number of bioactive protein drugs approved for clinical use each year, there is increasing need for vehicles for localized protein delivery to reduce administered doses, prevent off-target activity, and maintain protein bioactivity. Ideal protein delivery vehicles provide high encapsulation efficiency of bioactive drug, enable fine-tuning of protein release profiles, are biocompatible, and can be administered via minimally-invasive routes. Here we developed an approach to create micron-sized hydrated gels (i.e. “microgels”) for protein delivery that fulfill these requirements via desolvation of self-assembled β-sheet peptide nanofibers.  The desolvating agent induced nanofiber physical crosslinking into microgels that retained β-sheet secondary structure and were stable in aqueous solutions. Biocompatible microgels formed via desolvation of self-assembled peptide nanofibers are therefore likely to be broadly useful as vehicles for localized delivery of bioactive proteins, as well as other therapeutic molecules.

The Journal of Materials Chemistry B is part of the Royal Society of Chemistry Publishing, focusing on the materials field. The journal is interdisciplinary, publishing work of international significance on all aspects of materials chemistry related to biology and medicine.