Amy Lee Named 2017 Searle Scholar

Figure from Amy Lee

Assistant Professor of Biology Amy Si-Ying Lee was named a 2017 Searle Scholar, receiving $300,000 in flexible funding to support her work over the next three years. Lee’s research is focused on discovering how gene regulation occurs through novel mechanisms of mRNA translation. Specifically, her lab studies how non-canonical translation pathways shape cell growth and differentiation, and why defects in mRNA translation lead to developmental disorders and cancer.

Lee, who came to Brandeis in Summer 2016, has a PhD form Harvard and did her postdoc at UC Berkeley. She has also been awarded a 2017 Sloan Research Fellowship and in January won the Charles H. Hood Foundation Child Health Research Award. Lee’s lab is up and running and recruiting postdocs and PhD students (through the Molecular & Cell Biology and Biochemistry & Biophysics graduate programs). In Fall 2017, Lee will teach BIOL 105, Molecular Biology.

Amy Lee Joins Biology Faculty

On August 1, Amy Lee joined the Biology department as an Assistant Professor. Previously, Amy was an American Cancer Society Postdoctoral Scholar in Jamie Cate’s lab at University of California, Berkeley. She received her Ph.D. in Virology from Harvard University in Sean Whelan’s lab and her Bachelors of Science in Biology from Massachusetts Institute of Technology.


eIF3d structure, see Figure 2 at

Amy’s research focuses on understanding how gene regulation shapes cell growth and differentiation, and how dysregulation leads to human diseases like carcinogenesis and neurodegeneration. She is interested in discovering new mechanisms of mRNA translation initiation and novel functions of RNA-binding proteins and eukaryotic translation factors. Her research combines genome-wide and computational approaches together with molecular genetics, cell biology, biochemistry, and structural biology techniques.

Amy recently published a paper in Nature together with the Jamie Cate, Jennifer Doudna, and Philip Kranzusch describing the discovery of a new translation pathway that controls the production of proteins critical to regulating the growth and proliferation of cells. Cancer is characterized by uncontrolled cell growth, which means the protein production machinery goes into overdrive to provide the building materials and control systems for new cells. Hence, biologists for decades have studied the proteins that control how genes are transcribed into mRNA and how the mRNA is read and translated into a functioning protein. One key insight more than 40 years ago was that a so-called initiation protein must bind to a chemical handle on the end of each mRNA to start it through the protein manufacturing plant, the ribosome. Until now, this initiation protein was thought to be eIF4E (eukaryotic initiation factor 4E) for all mRNAs.

Amy and her colleagues discovered that for a certain specialized subset of mRNAs – most of which have been linked somehow to cancer – initiation is triggered by a different protein, called eIF3d. The finding was a surprise because the protein is part of an assembly of 13 proteins called eIF3 -eukaryotic initiation factor 3 – that has been known and studied for nearly 50 years, and no one suspected its undercover role in the cell. This may be because eIF3’s ability to selectively control mRNA translation is turned on only when it binds to the set of specialized mRNAs. Binding between eIF3 and these mRNAs opens up a pocket in eIF3d that then latches onto the end-cap of mRNA to trigger the translation process. Subsequent X-ray crystallography of eIF3d revealed the structural rearrangements that must occur when eIF3 binds to the mRNA tag and which open up the cap-binding pocket. eIF3d thus presents a promising new drug target in cancer, as a drug blocking this binding protein could shut off translation of only the growth-promoting proteins and not other life-critical proteins inside the cell.

Lee AS, Kranzusch PJ, Doudna JA, Cate JH. eIF3d is an mRNA cap-binding protein that is required for specialized translation initiation. Nature. 2016.


DUB inhibitors _or_ why you should you eat your broccoli

Eat your broccoli!

We’re constantly bombarded by advice on which foods to eat or not eat, but skeptics among us often find compelling evidence for a convincing mechanism of how the foods promote health hard to come by – food has many components, and there are many different cells and metabolic pathways in those cells with which those components interact.

phenethyl isothiocyanate (a component of cruciferous vegetables)

phenethyl isothiocyanate (PEITC, a component of cruciferous vegetables)

Consider broccoli. It is well established that cruciferous vegetables have wide-ranging health benefits, apparently reducing cancer risks and lowering inflammation.  One set of phytochemicals responsible for the potent anti-cancer and anti-inflammatory properties are called isothiocyanates or ‘ITCs’.  It is now four decades since the discovery of ITCs, yet a molecular understanding of what ITCs do in a cell has proven elusive.

In a paper published this month in Cancer Research, Brandeis research scientist Ann Lawson, working in Liz Hedstrom’s laboratory, together with graduate students Marcus Long (Biochem) and Rory Coffey (Mol Cell Biol) and scientists from UbiQ and from Boston College, has shown that ITCs block the action of deubiquitinating enzymes (DUBs),  including the tumorigenesis-associated enzymes USP9x and UCH37, at physiologically relevant concentrations and time scales.

DUB inhibition provides a simple, unifying explanation that can account for many of the diverse health effects of ITCs. Understanding of how ITCs work at the molecular level may, one day, lead to new drug therapies for illnesses such as cancer, chronic inflammation, and neurodegenerative diseases.

Are you ready for your broccoli now? Me, I think I’ll have some kale sprouts.

Lawson AP, Long MJ, Coffey RT, Qian Y, Weerapana E, El Oualid F, Hedstrom L. Naturally occurring isothiocyanates exert anticancer effects by inhibiting deubiquitinating enzymes. Cancer Res. 2015

Med School and Grad School in the Lone Star State

Wensink lab alum Mien-Chie Hung (PhD ’84), who is currently Ruth Legett Jones Distinguished Chair at  The University of Texas MD Anderson Cancer Center, will give seminar on Monday, Dec 3 at noon in Rosenstiel 118 on “Novel signaling pathways in cancer cells and their crosstalk to predict resistance for target therapy“.  He will also meet with interested students on Monday Dec. 3 in the Alumni Lounge in Usdan at 7 PM; there will be pizza.   He will talk with undergrads, prospective grad and med students about medical schools and graduate schools in Texas Medical Center including MD Anderson, UT Health Science Center and Baylor.

Unraveling mutations in pediatric brain cancer

Medulloblastoma is the most common malignant brain tumor of childhood, with an overall mortality of 40 to 50 percent. Surviving children often have significant long-term cognitive and physical sequelae resulting from existing treatments. Therefore, identifying and understanding the genetic events that drive these tumors is critical for the development of more effective therapies.

In the 2 August issue of the journal Nature, Brandeis Biochemistry faculty member Daniel Pomeranz Krummel contributed his structural biological expertise in collaboration with colleagues at Children’s Hospital Boston, Dana-Farber Cancer Institute, Harvard University, the Broad Institute (MIT), Stanford and the Hospital for Sick Children in Toronto. The paper titled, “Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations,” unravels a landscape of mutations that are peculiar to medulloblastomas. This paper represents a landmark study of medulloblastomas. More specifically, Pomeranz Krummel’s collaborators noticed that a protein called DDX3X had numerous mutations in medulloblastoma. Pomeranz Krummel was able to create a structural model of DDX3X that provided insight into the functional significance of the critical mutations in children with medulloblastoma (below, image).

DDX3X is an ATP-dependent RNA helicase. RNA helicases are fascinating proteins that function to drive the restructuring of RNA and/or RNA-protein assemblies, and have proven to be of great importance in cancer biology and HIV research. Pomeranz Krummel’s long-standing interest is in RNA-protein interactions and application of methods to visualize the enzymes critical to processing of RNA in the human cell. Thus, thinking about the structure-function relationship of this RNA helicase DDX3X was a problem of much interest to Pomeranz Krummel. This collaboration involved forging links between basic and translational scientists, thus giving rise to promising new horizons of treatment options for children with medulloblastoma.



James P. Allison to deliver Gabbay Award Lecture

James Allison, PhD  from the Memorial Sloan-Kettering Cancer Center will receive the 2011 Jacob Heskel Gabbay Award in Biotechnology and Medicine “for his development of strategies for the treatment of autoimmune diseases and for immunotherapy of cancer”. The award, administered by the Rosenstiel Center at Brandeis, consists of a $15,000 cash prize and a medallion. Dr. Allison will deliver the award lecture on Mobilizing the immune system to treat cancer: Immune checkpoint blockade, on Monday, Nov 14, 2011 at 3:30 pm in Gerstenzang 121.

Allison and his lab are interested in the mechanisms that regulate T cell responses and using that understanding to improve clinical outcomes in areas ranging from autoimmunity, to allergy to vaccination to  tumor therapy.

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