In the News
Martin to Join International Team Looking to Revolutionize mRNA Vaccines and Therapeutics
Craig Martin, professor of chemistry at the University of Massachusetts Amherst, will lead a UMass team that will spend the next three years developing a process that can deliver the quantity and quality of messenger RNA (mRNA) demanded by a new class of medicines, including the COVID vaccines, faster, cheaper and more effectively than any other method. Martin and his colleagues will be joining Wellcome’s R3 program, which seeks to create a global network of “biofoundaries” capable of producing high quality, low-cost mRNA, increasing global access to these new therapies, wherever they’re needed.
Martin whose co-principal investigators include Sarah Perry and Shelly Peyton, both professors of chemical engineering at UMass Amherst, is at the cutting edge of a new approach to medicine. Traditionally, illnesses have been cured by medicines that come from outside the human body: herbs, chemicals and vaccines. Recently, there’s been a new approach, using biologics, or therapies that delivers missing proteins to the human body and which can be used to treat a very wide range of illnesses that result from missing or damaged cell proteins.
But, says, Martin, this process can be taken one step further. “Instead of making the protein in some other organism and delivering it to humans,” he says, “we can make the RNA that encodes the protein, deliver that RNA as the biologic, and the patient’s own cells then make that protein from the delivered RNA.” The result is that, when the body makes the protein itself, “everything gets done correctly.” Furthermore, says Martin, “once you know how to make the RNA for one disease, it’s comparatively easy to swap in a different RNA so it can treat another disease. You don’t have to reinvent the wheel, saving money, and, crucially, saving time.”
If RNA therapies have not yet reached their full potential, it’s because making RNA that is pure enough, in great enough quantities, has proved very difficult—and the purity is of utmost importance. Impure RNA looks, to the body’s immune system like an invader and triggers an immune response. “This is actually ok for vaccines,” says Martin, “because what vaccines do is train the body’s immune system to recognize disease."
For certain diseases, though, especially those that are caused by genetic deficiencies, and for which the immune system plays no role, purity is important. Take cystic fibrosis, for example. Impure RNA would cause swelling in the lungs, making it even harder for a patient to breathe—a potentially deadly complication. Many cancers, too, are the result of genetic malfunctions, and could be treated with RNA therapies.
Martin, whose lab has been studying RNA for more than 30 years, has developed an approach to making RNA that employs a “flow reactor.” This method results in much larger quantities of much purer RNA. It is also scalable and can provide small amounts of RNA that could, for instance, address a particular person’s cancer, as well as the enormous amounts needed for something like a COVID vaccine.
While the Martin and Perry labs have already developed an initial smaller-scale version of their process, Perry and Peyton will help refine the process and be responsible for helping to scale the initial to industrial uses. “The microfluidic aspects of this technology rely critically on their small size,” Perry says. “Therefore, we will not ‘scale up’ so much as ‘scale out,’ creating many parallel reactors that can operate simultaneously to produce sufficient product for commercial use.” This scaling out, says Peyton, relies on a series of porous scaffolds, which Perry will engineer. Peyton will incorporate these porous scaffolds into the reactors. “Without both,” she says, “such an ambitious goal of continuous production of long mRNAs would not be possible.”
The work is part of the larger Wellcome Foundation’s Leap Health Breakthrough Network, a web of more than 70 world-class institutions, non-profits and commercial entities representing a network of over 650,000 scientists and engineers across six continents and is supported by a major grant. Early support for this work was provided by UMass Amherst’s Institute for Applied Life Sciences (IALS), which combines deep and interdisciplinary expertise from 29 departments on the UMass Amherst campus to translate fundamental research into innovations that benefit human health and well-being.
Buz Awarded a PPG Fellowship
Enes Buz (Kittlestved Group) Awarded a PPG Fellowship Award for outstanding research in the area of materials chemistry. Research summary: Transition-metal doped metal oxide semiconductors, in particular Zn1-xMxO, have attracted tremendous interest as potential candidates not only for the semiconductor-compatible magnetic components for spintronic applications but also room-temperature magnetism. While ZnO is a diamagnetic semiconductor, introduction of magnetic dopants such as Fe imparts magnetism on ZnO. In the Kittilstved research group, I study on different methods to tune the oxidation state of Fe dopants in ZnO nanocrystals (NCs) in a controlled way which will allow us to control the properties of ZnO NCs in turn. With the support of the PPG fellowship, I will be furthering my studies to investigate and directly show the specific oxidation state of Fe in ZnO NCs by utilizing various dopant-specific spectroscopic techniques. This study will help us to shed light on the mechanism of magnetism in ZnO NCs and to develop materials of interest for magnetism-related applications.
Wang Awarded PPG Fellowship
Tongkun Wang (Auerbach Group) Awarded a PPG Fellowship Award for outstanding research in the area of materials chemistry. Research summary: People in Prof. Scott Auerbach’s group focus on the study of zeolites, which are atomic crystals formed by tetrahedral atoms like Si with bridging atoms like O. As noticeable members of molecular sieves, zeolites have interesting porous structures and channels. To better understand their formation mechanism, we performed periodic density functional theory simulations and probed key precursors. Combined with experimental results from our collaborators, we successfully used Raman spectroscopy and thermodynamics calculations to reveal defects and explained why or why not they can be healed with the presence of organic structure directing agents. In future works, I will extend my ab initio molecular dynamics simulations in aqueous environment and study processes from monomers, via important building units, to full crystalline, which will help us to predict and design the synthesis for zeolites we want.
Lecture Hall Named After Alumnus Augustine "Gus" Silveira
Martin Wins Innovation Award
The University of Massachusetts Amherst’s Institute for Applied Life Sciences (IALS) has announced that six campus research teams have been named recipients of the 3rd annual Manning/IALS Innovation Awards. These translational grants are designed to advance applied research and development efforts from UMass-based faculty research groups in the sciences and engineering through the development of spin-out/startup companies and the out-licensing of UMass intellectual property.
Alumnus Paul Manning and his wife, Diane, committed $1 million through their family foundation to establish the Manning Innovation Program. The gift provides three years of support in advancing a robust and sustainable commercialization pipeline of applied and translational research projects from UMass Amherst.
Peter Reinhart, founding director of IALS, says, “We are grateful to the Manning Family Foundation and Paul Manning for their support of this exciting translational initiative. This seed fund program enables UMass Amherst start-up companies to traverse the funding ‘valley of death’ towards success.”
Six projects were selected from a highly competitive group of applicants. Each successful team will receive seed funding of up to $100,000 over 12 to 18 months towards achieving translational milestones. In addition, a collaborative effort from IALS, the College of Natural Sciences, the Berthiaume Center for Entrepreneurship and the Isenberg School of Management will provide support for commercialization efforts, including business training and mentorship resources.
The winning team leaders and their projects are:
- RNA4Therapeutics: Craig Martin, chemistry. A novel manufacturing technology for the synthesis of high purity, low-cost, and large scale RNA manufacturing for therapeutic use.
- E2-PATH: Karen Dunphy/Joe Jerry, veterinary & animal sciences. A diagnostic personalized medicine screening platform for selecting optimized breast cancer treatments.
- OPG Wastewater Treatment: Chul Park, civil & environmental engineering. Developing technology that enables aeration-free and energy efficient wastewater treatment.
- Optical Waters: Mariana Lopes, civil & environmental engineering. Germicidal optical fibers to prevent disease causing biofilms in medical devices.
- 3Daughters: Carlos Gradil, veterinary & animal sciences. A women’s healthcare startup developing a new ergonomic, pain-free, magnetic intrauterine device (IUD).
- Volvox Sciences: Ashish Kulkarni, chemical engineering. Developing a novel supramolecular nano-therapeutic (CSF-SNT) that can efficiently remove cancer tumor cells.
The award process brought together on-campus and off-campus reviewers of these applications. The reviewers bring diverse perspectives with science, engineering, nursing, public health and health sciences, and data/computer science expertise and were supplemented by industry/start-up and IP expertise. The project was supported by Manning-IALS Summer Business Innovation Fellows.
“The Manning Innovation Awards are the perfect catalyst for forging collaborative effort across campus disciplines in support of moving ground-breaking science from our labs to our community,” says Tricia Serio, dean of the College of Natural Sciences and associate chancellor for strategic academic planning. “This investment again supports UMass as a partner of choice in advancing and generating new knowledge, leading to the betterment of society.”
“At UMass, we are dedicated to finding solutions to real-world problems that impact society and our planet,” says Sanjay Raman, dean of the College of Engineering. “The Manning/IALS innovation awards represent a vital investment in taking science and engineering discoveries from lab to market. We are incredibly proud of this year’s winners and are looking forward to seeing these exciting projects move forward on the path to commercialization.”
Paul Manning, a 1977 graduate of UMass Amherst, is an entrepreneur with 30 years of experience in the healthcare industry, who most recently founded PBM Capital Group in 2010. It is a healthcare-focused private investment group that looks for opportunities to use its entrepreneurial and operational experience to make high-growth pharmaceutical, molecular diagnostic, gene therapy, life science, health/wellness and consumer product investments.
Manning was also the anchor investor in Maroon Venture Partners, the first venture-capital fund at UMass Amherst. Created in 2017, the fund is a $6 million for-profit investment vehicle created to support alumni, faculty, and student businesses in their early stages.
IALS was established in 2014, supported by a total investment of more than $150 million from the Massachusetts Life Science Center and the campus. The Manning-IALS partnership has enabled a total of 18 UMass-based translational projects since 2019.
Lu-Diaz Awarded Donald Kuhn Graduate Fellowship
Michael Lu-Diaz (DV group) Awarded the Donald Kuhn Graduate Fellowship for outstanding reseaarch, and an interest in pursuing a career in research or teaching.
Research Summary: Chemically doped conjugated polymers comprise a myriad of applications among organic electronics. The chemical doping process consists of introducing a molecule to partially oxidize or reduce a polymer's backbone and create a charge. Although this charge is presumed to be mobile, it experiences a strong, attractive Coulomb interaction with a dopant, ultimately affecting charge transport. I am studying methods to screen this Coulomb interaction and help this charge move. Our experiments and models indicate that the dielectric permittivity is a tunable and crucial parameter to reduce polymer-dopant Coulomb interactions. We used a charge hopping model and fabricated polymer composites with nanocrystals with tunable dielectric permittivity. Ongoing studies focus on understanding how different physical properties of a polymer impact polymer-dopant Coulomb interactions to create more efficient materials.
Zhang Awarded Marvin D. Rausch Fellowship
Xianzhi Zhang (Rotello Group) Awarded the Marvin D. Rausch Fellowship for outstanding research in the area of organic or inorganic chemistry.
Research Summary: Bioorthogonal chemistry uses abiotic chemical processes to create a new toolkit for biological and biomedical applications. Bioorthogonal catalysis via transition metal catalysts (TMCs) provides a particularly promising direction that employs the high catalytic activity and chemical specificity inherent in TMCs. The direct application of TMCs in living cells is challenging due to the generally poor water solubility and instability of these hydrophobic catalysts in biological environments. In the Rotello lab, these issues can be addressed by incorporating TMCs into nanomaterials to generate bioorthogonal “nanozymes”. Nanozymes can activate imaging and therapeutic agents from their inactive precursors, creating on-demand “drug factories”. By engineering surface functionality and size of nanomaterials, I synthesized various nanozymes with biostability and/or stimuli responsiveness. Furthermore, I also designed and synthesized a library of substrates for nanozymes to broaden their applications for bioimaging, cancer chemotherapy and immunotherapy. The therapeutic potential of nanozymes was demonstrated both in vitro and in vivo, creating an anti-cancer treatment with increased efficacy and reduced side effects.
Rotello Remains on the List of Highly Cited Researchers
UMass Chemistry Faculty Search
Assistant Professor - Chemistry - DNA/RNA: The Department of Chemistry, along with the Center for Bioactive Delivery within the Institute for Applied Life Sciences, (IALS, https://www.umass.edu/cbd/) invites applications for a full-time, tenure track faculty position. As the development of new therapeutic molecules shifts toward biologics, we seek applicants who will develop an innovative translational research program focused on the development and/or delivery of therapeutic nucleic acids and/or other functional biologics. Associated topics of interest include, but are not limited to, developing stable versions of biologics and smart delivery of macromolecular therapeutics to target locations. Full description and details.
Ostrander Receives NSDEG Fellowship
Eric Ostrander from the DV Research Group has been selected to receive the National Defense Science and Engineering Graduate Fellowship (NSDEG). The DoD NDSEG Fellowship Program is highly competitive and provides three years of funding to focus on research aligned with the interests of the DoD. Eric’s research focuses on gaining further insight into the factors which allow for adenosine triphosphate (ATP) to be selectively used as the energy molecule for muscle function. By using various abiotic triphosphate compounds, Eric probes the role of aromatic stacking interactions and hydrogen bonding on the function of myosin, a molecular motor that transduces chemical energy into mechanical work. The end goal here is to develop innovative synthetic substrates and molecular design paradigms to control the activity of myosin.
You Receives Burlew Award
Assistant Professor Mingxu You was awarded the 2020-21 John S. Burlew Award from the Connecticut Valley Section of the American Chemical Society (CVS-ACS). The Burlew Award was established in 1986 to “recognize outstanding contributions to chemistry by CVS-ACS members”. Dr. You has been recognized for his significant contribution in DNA and RNA nanotechnology and has co-authored over 75 journal articles and 3 book chapters in this field.
