Michael B. Yaffe

News + Videos

Clinical Cancer Research

KI researchers hog the covers

October was a big month for KI research, with two publications featured as journal cover stories. In Clinical Cancer Research, researchers from the labs of Paula Hammond, David H. Koch Professor of Engineering, and Michael Yaffe, David H. Koch Professor of Science, describe a nanoscale drug formulation engineered with Hammond’s layer-by-layer technology. The nanoparticles simultaneously block two key cell signaling pathways in an animal model of breast cancer, thus evading drug resistance and enhancing cancer-cell death. Meanwhile, in Genes & Development, researchers from the lab of Angelika Amon, the Kathleen and Curtis Marble Professor in Cancer Research, report a new link between aneuploidy — the presence of an abnormal number of chromosomes, often found in cancer cells — and lysosomal stress due to an overload of aggregated proteins. more...

crystal structures of p53 DNA-binding domains

Yaffe Lab backs cancer into a corner

Researchers in the laboratory of KI faculty member Michael Yaffe have discovered a drug-resistance mechanism in tumor cells: a backup system that takes over when p53 is disabled. By targeting this backup system, these tumors could be made much more susceptible to chemotherapy. more...

Double Trouble for Aggressive Cancers

KI researchers led by Paula Hammond, David H. Koch Professor of Engineering, and Michael Yaffe, the David H. Koch Professor of Science, have engineered new, “smart” nanoparticles that directly target tumor cells to deliver multiple drugs in a staggered, precisely-timed regimen.

In 2012, the Yaffe Lab showed that the timing of drug administration can make a great difference in the success of combination treatments. Yaffe’s team discovered that pre-treating tumor cells with erlotinib, a therapeutic that shuts down uncontrolled tumor growth, before administering a DNA-damaging agent called doxorubicin, is more effective than giving the two drugs simultaneously.

As part of efforts to adapt the findings for patient care, Yaffe enlisted the help of KI colleague Paula Hammond. Hammond and her team designed dozens of nanoparticles to carry Yaffe’s treatment and found that liposomes, small droplets covered in a fatty shell, were most effective. With the first drug, erlotnib, injected in the outer layer, and the second, doxorubicin, contained in the inner core, the liposomes dispatched treatment to the cells at ideal intervals as the particles broke down in the body. In the study, published in Science Signaling, this treatment was shown to effectively knock out triple-negative breast tumors and non-small-cell lung tumors in mouse models. The researchers hope to expand time-staggered treatment to other types of chemotherapy.

This work was supported in part by the Koch Institute Frontier Research Program through the Kathy and Curt Marble Fund for Cancer Research. more...

Opening Remarks

Michael Yaffe, Koch Institute for Integrative Cancer Research at MIT watch...

Yaffe Finds New Target for Cancer Combination Treatment

Mutation of the p53 gene occurs in about half of all cancer patients, and tumors with the mutation continue growing even after intense chemotherapy. Previously, the lab of Michael Yaffe, David H. Koch Professor of Biology and Biological Engineering, discovered that blocking a gene called MK2 can overcome the effects of the p53 mutation and make these tumors more vulnerable to chemotherapy in vitro. In a new study published in Cell Reports, Yaffe lab researchers collaborated with KI Director Tyler Jacks to create mice with MK2 genes that can be turned on and off and test the process in vivo. They found that in p53-deficient tumor-bearing mice with MK2 turned off, tumors shrank successfully upon treatment with the DNA-damaging therapeutic cisplatin, whereas tumors in mice with unblocked MK2 genes continued growing. This study suggests potential for new cancer treatments combining MK2 inhibitors with DNA-damaging drugs. Drugs that inhibit MK2 are in the works for other diseases such as arthritis, but this is the first time they are being considered for cancer therapy. The research was primarily funded by a TRANSCEND grant from Janssen Pharmaceuticals, Inc.
The study was profiled in MIT Technology Review. more...

Yaffe Attempts Special Engineering Feat For KI

Michael Yaffe, David H. Koch Professor in Biology and Biological Engineering, is a notable biologist, engineer, entrepreneur, physician, military trauma surgeon, and dad. On September 16, 2013 from 6-8PM, Professor Yaffe will publicly test whether all his skills are enough to construct that biologically heterogeneous, composite-layered cylindrical marvel known as the burrito. Yaffe will roll as part of the Anna's Taqueria Celebrity Burrito Roller Series at Anna's MIT location in the Stratton Student Center. Burritos are $10 each, with the full amount going to benefit KI programs and research.  This may be the tastiest way ever to support the KI! more...

Sequence Matters: mTORC1 Phosphorylation Sites and Rapamycin

The drug rapamycin, a partial inhibitor of the kinase subunit of the protein complex mTORC1, can slow cancer cell growth and prolong life span. In a new Science publication, a collaborative team led by KI members David Sabatini and Michael Yaffe shows that the characteristics, including sequence composition, of the sites that are phosphorylated by mTORC1 determine how efficient the phosphorylation is and the sensitivity of the process to rapamycin inhibition and starvation within cells; the more efficient the phosphorylation, the more resistant it is to rapamycin inhibition and starvation.  These results may explain the weak efficacy of the drug in several early cancer clinical trials. more...

Cancer Treatment Challenges Symposium/Roundtable

At this May 6, 2013 event, cancer biologists, engineers, and clinicians gathered at the Koch Institute at MIT for an open discussion of the greatest challenges and most promising solutions in cancer care. Speakers included:

Phillip A. Sharp, Institute Professor, Koch Institute at MIT
Sangeeta N. Bhatia, John J. and Dorothy Wilson Professor of Health Sciences and Technology & Electrical Engineering and Computer Science, Koch Institute at MIT
K. Dane Wittrup, Carbon P. Dubbs Professor of Chemical Engineering and Bioengineering, Koch Institute at MIT
Michael B. Yaffe, David H. Koch Professor of Biology and Biological Engineering, Koch Institute at MIT
Catherine J. Wu, Associate Physician, Medical Oncology, Dana-Farber Cancer Institute
Jay S. Loeffler, Chief, Radiation Oncology, Massachusetts General Hospital
Matthew R. Smith, Director, Genitourinary Malignancies Program, Massachusetts General Hospital Cancer Center
Steven P. Balk, Staff Physician, Hematology/Oncology, Beth Israel Deaconess Medical Center Hear highlights from the discussion in the video below. The event also featured presentations by researchers working on existing Bridge Project teams: Christopher Love, Koch Institute at MIT, Hidde Ploegh, Whitehead Institute and Koch Institute at MIT, and Kai W. Wucherpfennig, Dana Farber Cancer Institute
Novel Immunotherapies Against Pancreatic Cancer Elazer Edelman, Institute of Medical Engineering and Sciences at MIT and Koch Institute at MIT and Jeffrey W. Clark, Massachusetts General Hospital
A Pancreatobiliary Chemotherapy Eluting Stent for Pancreatic Ductal Adenocarcinomas Rakesh K. Jain, Massachusetts General Hospital and Robert Langer, Koch Institute at MIT
Angiotensin Receptor Blockers (ARBs) as a Novel Approach to Improve Drug Delivery in the Treatment of Pancreatic Cancer Keith L. Ligon, Dana-Farber Cancer Institute and J. Christopher Love, Koch Institute at MIT
Single-Cell Functional, Genomic and Transcriptomic Analysis in Glioblastoma watch...

Technology Workshop: Michael Yaffe

September 20, 2012 Systems Bio
Michael Yaffe, Koch Institute watch...

Staggered Drug Delivery Shows Promise in Treating Aggressive Breast Cancer

KI member Michael Yaffe and his laboratory team report finding, in the May 11 issue of Cell, that staggering the doses of two common cancer drugs dramatically boosts their ability to kill a particularly malignant type of breast cancer cells. Yaffe has been studying the complex cell signaling pathways of cancer cells and the ability of dysfunctional pathways to promote uncontrolled cell growth. He is now working with researchers at Dana Farber Cancer Institute to plan clinical trials of the novel approach. more...

AAAS Science reviews and looks at future of science signaling with KI faculty member

A conversation with Michael B. Yaffe about research articles published in Science Signaling in 2009. more...

Modeling and Personalizing Cancer 2

Michael B. Yaffe, Professor of Biology and Biological Engineering watch...

Tumor mutations can predict chemo success

New work by MIT cancer biologists shows that the interplay between two key genes that are often defective in tumors determines how cancer cells respond to chemotherapy. The findings should have an immediate impact on cancer treatment, say Michael Hemann and Michael Yaffe, the two MIT biology professors who led the study. The work could help doctors predict what types of chemotherapy will be effective in a particular tumor, which would help tailor treatments to each patient. more...

New KI computational models to individualize cancer treatment

In Cell, KI researcher describe how computer simulations can reveal the inner workings and vulnerabilities of a cancer. The results reveal new ways in which cells process chemical information and could indicate how to maximize the effectiveness of disease treatments such as chemotherapy. more...