We wanted to share some recent Massachusetts General Hospital research that has been published in high impact, top-tier journals. This is just a small snapshot of the incredible research that takes place at Mass General each day — there’s lots more to find on the Mass General website!
Cognitive Decline, Tau and β-Amyloid in Healthy Older Adults
(Summary submitted by Rachel Buckley, PhD, and Rebecca Amariglio, PhD, both of the Martinos Center for Biomedical Imaging)
We published findings from the Harvard Aging Brain Study (Department of Neurology, Massachusetts General Hospital) investigating the link between subjective memory complaints (when a patient reports a worsening of their thinking abilities, including memory) and Alzheimer’s disease pathology in individuals who are otherwise cognitively normal. We found that increasing memory complaints were linked with greater amounts of tau in the brain, a naturally occurring protein that is associated with neuron loss in Alzheimer’s disease. We posit that memory complaints are a very early marker of disease, as they relate to tau build up before clinical tests can detect memory impairment.
Region-Specific Association of Subjective Cognitive Decline With Tauopathy Independent of Global β-Amyloid Burden
Buckley RF, Hanseeuw B, Schultz AP, Vannini P, Aghjayan SL, Properzi MJ, [et al.] Amariglio RE
Published in JAMA Neurology on October 2, 2017
New Approach to Targeted Cancer Treatment
(Summary submitted by Conor L. Evans, PhD, of the Wellman Center for Photomedicine)
We have created a promising new light-activated, cancer-targeting therapeutic. Cancer drugs often cannot reach every cell in a tumor, leaving behind cells that can become resistant to treatment. At the same time, these drugs can cause unwanted systemic problems, such as weight and hair loss, elsewhere in the patient’s body. Our therapeutic was built to diffuse throughout tumors, target cancer cells, and kill these cells only when activated by light to avoid unwanted and burdensome side effects. We hope that this approach could one day find use in the fight against treatment-resistant cancers, like breast and lung.
An Integrin-Targeted, Highly Diffusive Construct for Photodynamic Therapy
Klein OJ, Yuan H, Nowell NH, Kaittanis C, Josephson L, Evans CL
Published in Scientific Reports on October 17, 2017
Identifying Genes that Help Protect the Gut
(Summary submitted by Javier Elbio Irazoqui, PhD, formerly of the Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease)
The intestinal epithelium is a single layer of cells that protects the gut from environmental insult. Defects in this layer are linked to many diseases, including inflammatory bowel disease. Despite its critical importance, very little is known about the genes in the epithelium involved in this function. We found that transcription factor TFEB, a master regulator of lysosomal gene expression, provides a protective effect, and this function is mediated by expression of apolipoprotein A1, the major constituent of HDL, aka “good” cholesterol. Our findings suggest that enhancement of TFEB activity in the intestinal epithelium could be a therapeutic approach to enhance Apolipoprotein A1 expression for the treatment of inflammatory bowel disease.
Transcription Factor TFEB Cell-Autonomously Modulates Susceptibility to Intestinal Epithelial Cell Injury In Vivo
Murano T, Najibi M, Paulus GLC, Adiliaghdam F, Valencia-Guerrero A, Selig M, [et al.] Xavier RJ, Lassen KG, Irazoqui JE
Published in Scientific Reports on October 24, 2017
Patient Resistance to Immune Checkpoint Blockade Therapies
(Summary submitted by Nir Hacohen, PhD, of the Cancer Center)
Cancer therapy has been transformed in the last few years by immune-based therapies, called ‘checkpoint blockade’ therapies. An important question is why some people respond and others do not respond to this therapy. By analyzing the DNA of tumors from patients who developed resistance to checkpoint therapy, we found changes in the DNA of a key gene that is critical for tumors to be detected by the immune system. In this way, the tumor has learned how to hide from the immunotherapy. Knowing this will help us decide which patients would benefit from immune therapy. Finding ways to make these resistant tumors visible to the immune system is an important goal for the coming years.
Resistance to Checkpoint Blockade Therapy Through Inactivation of Antigen Presentation
Sade-Feldman M, Jiao YJ, Chen JH, Rooney MS, Barzily-Rokni M, Eliane JP, [et al.] Flaherty KT, Sullivan RJ, Hacohen N
Published in Nature Communications on October 26, 2017