PhD student Hanan Alwaseem, in the lab of Rudi Fasan, associate professor of chemistry, demonstrates how she produces analogs of a new compound the lab has developed as a potential treatment for acute myeloid leukemia. (Photo by Bob Marcotte / University of Rochester)
Seed grant enables researchers to try new approach to targeting leukemia
(The first in a series looking at promising research projects being supported by the University Research Award program.)
University researchers hope to improve the odds of surviving acute myeloid leukemia (AML) with a promising drug that traces its lineage to a chemical found in magnolias. They will load the drug into nanoparticles that will target the inner recesses of bone marrow where leukemia stem cells lurk.
Team members Rudi Fasan, associate professor of chemistry; Danielle Benoit, associate professor of biomedical engineering; and Benjamin Frisch, research assistant professor of hematology and oncology, are supported by a $75,000University Research Award. The award program is one of several University “seed grants” (see also PumpPrimer II awards below) that help investigators develop preliminary data and proof of concept for promising projects, in hopes of leveraging larger awards from federal agencies or foundations to carry the projects to fruition.
The low survival rates for AML, especially among older patients, and the limited treatment options when the disease relapses constitute “one of the major challenges in leukemia,” Fasan says. Even after the bulk of active leukemia cells in the bloodstream are destroyed by an initial round of chemotherapy, he says, a “quiescent” subpopulation of leukemia stem cells often survives in the bone marrow.
When the stem cells enable the cancer to repopulate during a relapse, the newly emerged cancer is often more aggressive and more resistant to treatment.
“What is important is to be able not only to target leukemia cells selectively, but also to eradicate cancer stem cells as well,” Fasan says. He believes the researchers and labs collaborating on the project are particularly well suited to take on the challenge, bringing to bear expertise in organic and medicinal chemistry (Fasan), drug delivery technologies (Benoit), and the physiopathology of bone marrow during myeloid malignancy (Frisch).
For example, Fasan’s lab has worked for several years with chemical compounds extracted from plants, further refining them as anticancer agents. One such compound is micheliolide, derived from a naturally occurring chemical that makes magnolia leaves unpalatable to insects. Using a combination of engineered enzymes and chemical methods, Fasan’s lab has further modified micheliolide to develop analogs – or variants – with improved activity against both active leukemia cells and leukemia stem cells.
“We can generate entire libraries of this compound,” says Fasan. His team is working with Frisch on testing which analogs are most effective, and at which doses, when applied to an acute myeloid leukemia cell line used in the Frisch lab.
An illustration from the Benoit lab shows how it forms nanoparticle drug delivery vehicles. Polymers containing both hydrophilic (water attracting) and hydrophobic (water repelling) portions are synthesized. When the polymers are introduced to a water-based solvent, the particles form nanometer-sized micelles (nanoparticles). Drugs are loaded into the micelles, and targeting moieties selected to target bone marrow are conjugated to the outside, to provide preferential drug delivery to marrow-resident stem cells.
Benoit’s lab, in the meantime, has been developing polymer nanoparticles as vehicles for delivering chemotherapeutic drugs to specific parts of the body where a disease occurs, in order to minimize damage to healthy tissues.
Her lab recently augmented the nanoparticles with a peptide that can help steer the drug vehicles specifically to bone marrow. The peptide binds to the TRAP enzyme that is released when diseased or worn bone tissue is broken down by osteoclasts during the body’s ongoing process of bone remodeling. The remodeling activity is especially prevalent in the marrow of leukemia patients.
Preliminary studies show that the nanoparticles accumulate at a significantly higher rate in TRAP-positive bone tissue than other tissues, and can efficiently load and then gradually release a chemical compound similar to the one Fasan’s lab has developed.
Benoit’s lab will further test how the nanoparticles perform when loaded with analogs of Fasan’s compound, and adjust the nanoparticles accordingly.
Eventually, the two to three most promising nanoparticle-analog combinations will be tested on mice models that replicate AML in Frisch’s lab.
“The nice thing about these preclinical models is that they have well defined leukemia stem cell populations that we know reside in the bone marrow,” Frisch says. “So it provides a nice way to test the ability of these compounds after being loaded into the nanoparticles to actually target leukemia stem cells within the bone marrow.”
The award will support graduate students working on the project, and also help offset other costs, such as producing sufficient quantities of the compound analogs, optimization of the nanoparticle delivery system, and the cost of the mice used to model leukemia.
The program “is a great way to get some seed funding and to develop the preliminary data that will make you more competitive for NIH funding,” Benoit says. Frisch concurs.
And, as Fasan notes, the award enables three researchers with relevant expertise to work on a project that they would not have been able to pursue on their own. “The great aspect of this award is the opportunity to combine this expertise around a common interest, and really give this a shot, in terms of trying a new direction and seeing if it can leverage additional support.”
PumpPrimer II awards go to six researchers
Six AS&E researchers have been awarded PumpPrimer II awards by the Office of the Dean of Research.
They are:
Florian Jaeger, associate professor of brain and cognitive sciences, “Assessing and Developing Web-based Pronunciation Training for Second Language Learners.” Testing effectiveness of audio-visual feedback and use of crowdsourcing to assess learning progress.
Amy Lerner, associate professor of biomedical engineering, “Corneal Biomechanics and Optics, Model Refinement and Validation of Translational Applications.” Validating an advanced three-dimensional corneal biomechanical model.
Qiang Lin, assistant professor of electrical and computer engineering, “Undefined Lithium Niobate Nanophotonics for Ultra-high-speed Beam Ranging, Wavefront Engineering, and Photonic Signal Processing.” Exploring and developing innovatively designed lithium niobate nanophotonic circuits.
James McGrath, professor of biomedical engineering, “Desalinization with Ultrathin Nafion Membranes.”Testing a prediction that ultrathin Nafion membranes have the potential for desalinization with orders-of-magnitude greater efficiency than conventional reverse osmosis.
Daven Presgraves, Dean’s Professor of Biology, “Evolution of Sex Chromosome Regulation in the Drosophila Male Germline.” Understanding the phylogenetic distribution of X suppression — what other species do it besides D. melanogaster? New opportunities for comparative genomics analysis of X suppression.
James Zavislan, associate professor of optics, “Second-Generation Multimodal Ocular Surface Metrology.” Developing an ocular surface imaging system to measure factors related to dry eye disease and to assess treatments.
The increasingly competitive environment for extramural funding increases the need for proof of concept and/or pilot data in proposals and decreases funding of high-risk proposals. To help faculty secure extramural funding for bold new research directions, the Dean’s Office will provide PumpPrimer II funding of typically $1,000 to $20,000, and rarely as much as $50,000, for up to one year.
Successful applications must make a compelling argument that the research direction is truly innovative; applicants must have a strong track record of research productivity, and provide evidence that no alternative funds are available for the project.
Junior Women Research Faculty Group meets December 16
A Junior Women Research Faculty Group has been created to promote community among women at early stages of their careers.
The group holds seminars and skill-building workshops every other month to foster career development.
Catherine Cerulli, associate professor of psychiatry and director of the Susan B. Anthony Center, will lead an Individual Development Plan workshop at the next meeting at noon on December 16.
Click here to read more on the CTSI Stories Blog. For more information or to sign up for meeting announcements, contact Jennifer Gewandter.
Introducing a new faculty member . . .
William Miller has joined the Department of English as an assistant professor after earning his PhD from Johns Hopkins University. In his current book project, Counter-Enthusiasms: The Rationalization of False Prophecy in the Early English Enlightenment, he argues that unlicensed popular prophesying in the mid–17th century necessitated a thorough revision of the link between revelation and political legitimacy, resulting in new notions of language and rationality. Miller has served as managing editor of ELH: English Literary History and has taught on 17th- and 18th-century British literature; the novel; literature and language theory; the relation among religion, science, and literature; and other topics.
CTSI can help with applications for R21 awards
R21 awards support highly innovative, exploratory, collaborative research projects in the Clinical and Translational Science Award (CTSA) program, with the goal of assessing utility and feasibility of multihub projects.
Any faculty member is eligible to apply. The Clinical and Translational Science Institute will help, and can help find collaborating CTSA hubs.
Examples of fundable projects include, but are not limited to:
translational studies of the human microbiome
approaches to implementation science
use of wearable/mobile devices
evaluating methods of engaging communities in research
the use of telemedicine approaches in rare disease research
informatics and IT solutions
approaches to the collection and use of direct patient reported outcomes
The 21st Annual Wilmot Cancer Institute Scientific Symposium will be held from 9 a.m. to 4 p.m., Thursday, November 10, in the Class of ’62 Auditorium and the Flaum Atrium.
The purpose of the symposium is to bring together scientists working in basic, translational, and clinical cancer research.
Warner forum addresses black girls’ school experiences
The Warner School’s Urban Teaching and Leadership Program will present a forum on “Other People’s Daughters: Black Girls’ Experiences in P-12 Schools” at 5:30 p.m. Wednesday, November 16, in the Welles-Brown Room, Rush Rhees Library. The forum will examine the challenges that black girls face in P-12 schools and identify strategies for empowering black girls. Read more here.
Workshop shows how to prepare a poster
Denham Ward, professor emeritus of anesthesiology and of biomedical engineering, will present “How to Prepare a Poster for Presentation” from 11:30 a.m. to 1 p.m. November 30 in the Center for Experiential Learning (2-7544), Medical Center.
The session is part of a series of workshops in preparation for the 2017 Association of American Medical College’s Northeast Group on Educational Affairs annual conference to be held at the School of Medicine and Dentistry from May 4 to 6.
Imaging symposium focuses on immune response
The Second Immune Imaging Symposium will be held from 8 a.m. to 6 p.m. tomorrow, Saturday, November 5, in Saunders Research Building.
The Program for Advanced Immune Bioimaging hosts speakers presenting work on immunity to infection, inflammation, and tumors.
The meeting focuses on the use of cutting-edge techniques for in situ analysis of the dynamic actions of the immune response.
Ran Xin, Physics, “All-Fiber, Directly Chirped Laser Source for Chirped-Pulse-Amplification.” 2 p.m., Nov. 17, 2016. Bausch and Lomb 372. Advisor: Jonathan Zuegel.
Mark your calendar
Nov. 5: Second Immune Imaging Symposium, 8 a.m. to 6 p.m. Saunders Research Building. Hosted by the Program for Advanced Immune Bioimaging. Preregistration is advised. Visit immuneimagingsymposium.urmc.edu for more information.
Nov. 10: 21st Annual Wilmot Cancer Institute Scientific Symposium. 9 a.m. to 4 p.m., Class of ’62 Auditorium and the Flaum Atrium. Click here for more information.
Nov. 12: RocHD3: Rochester Healthcare Deep Data Dive, 8 a.m. to 5 p.m., Saunders Research Building. Read more here.
Nov. 14: Initial abstracts due for Incubator Program awards of up to $125,000 per year for each of two years to foster interdisciplinary research collaborations in biomedical research, through the Scientific Advisory Committee of the School of Medicine and Dentistry. Click here for more details. Contact Anne Reed for more information.
Nov. 16: “Other People’s Daughters: Black Girls’ Experiences in P-12 Schools,” forum sponsored by Warner School Urban Teaching and Leadership Program. 5:30 p.m. Welles-Brown Room, Rush Rhees Library. Read more here.
Nov. 16: Lecture: “A Pilgrimage to World War II Japanese-American Internment Camps.” Notch Miyake. 5 p.m., Gowen Room, Wilson Commons. Part of “Looking like the Enemy: The WWII Japanese American Experience” Humanities Project.
Nov. 17: Reception to begin exhibition of Margaret Miyake’s photographs as part of the “Looking like the Enemy: The WWII Japanese American Experience” Humanities Project. 5 p.m. Hartnett Gallery. Exhibit runs through Dec. 11.
Nov. 30: “How to Prepare a Poster for Presentation.” Denham Ward, professor emeritus of anesthesiology and of biomedical engineering. 11:30 a.m. to 1 p.m. Center for Experiential Learning (2-7544), Medical Center.
Dec. 1: Deadline to apply for Humanities Center semester-long fellowships for proposals that address the theme of “Memory and Forgetting.” To apply, click here.
Dec. 1: Center for AIDS Research eighth annual HIV/AIDS Scientific Symposium. Keynote addresses in the Class of ’62 Auditorium (G-9425) and a poster session from 11 a.m. to 12:30 p.m. in Flaum Atrium. Contact Laura Enders with questions or for more information.
Dec. 2: Applications due for Collaborative Pilot Studies and Junior Investigator Awards from the Wilmot Cancer Institute. Contact Pam Iadarola for more information.
