Keith Tornheim named Distinguished Faculty of the Month

May 2nd, 2022in Departmental News

Headshot of Dr. TornheimThe Faculty Affairs Office is pleased to announce that Associate Professor of Biochemistry Keith Tornheim, PhD, is May’s Distinguished Faculty of the Month.

Tornheim received his PhD in biochemistry from Brandeis University. He began his career at BUSM in 1981 as an assistant professor.

His nominators say, “Dr. Tornheim has contributed for 40 years to the teaching mission of Boston University School of Medicine. He currently teaches or has taught in the Medical School, Dental School, PhD, and MS programs. He has an unrivaled expertise in metabolic pathways and disease, and enzymology … and he is a fixture at our departmental and student/post-doc seminars. I am certain he has the best total attendance record of any member of our department!”

The nominators continued, “Keith is an advocate of the arts at BUSM; he is a faculty advisor of the Creative Arts Society and has both managed and contributed as a poet and sculptor to Art Days celebration for many years. Everyone on campus looks forward to this annual event. It is amazing to see the varied talents of our community and Keith’s efforts are a significant reason why these days continue.”

The 2021 Art Days theme was Antiracism, highlighting the creative BUMC community’s resolve to oppose racial hatred, bias and oppression of marginalized groups while promoting allyship, continued education and discourse. Tornheim contributed poems including Persistence of Inequality, Skin Deep, and Slave Memories.

Original article here

Congratulations to Bob Varelas on his promotion to Professor of Biochemistry

Congratulations to Bob Varelas on his promotion to Full Professor of Biochemistry!

Research in the Varelas lab is focused on gaining insight into molecular mechanisms that direct cell fate decisions during animal development, homeostasis, and disease. The lab is particularly interested in understanding the functions of the transcriptional regulators YAP and TAZ (YAP/TAZ), which are key effectors of Hippo pathway signaling, and uses molecular and genetic approaches to study these factors across various aspects of biology.

Congratulations to all the Biochemistry Faculty members awarded Dahod Pilot Grants

Congratulations to Alla Grishok, Valentina Perissi, Bob Varelas and Cathy Costello, who were all awarded Dahod Pilot Grants.

Alla Grishok, PhD, associate professor of biochemistry, studies the oncoprotein DOT1L, which is essential for triple negative breast cancer progression. DOT1L, localized to the nucleus, activates many genes driving uncontrolled cell divisions. The Grishok lab will study how different parts of the large DOT1L protein work together to activate cancer-promoting genes. This mechanistic work may suggest new approaches to inhibit DOT1L, a promising drug target for cancer treatment.

Valentina Perissi, PhD, associate professor of biochemistry, will study the molecular mechanism of PARP1 inhibition in human breast cancer cells. Poly-ADP ribosyltransferase inhibitors (PARPi) have emerged as promising drugs for the treatment of triple negative breast cancer and metastatic breast cancer. Understanding how PARP activity is endogenously restricted in cells will assist in determining the dosage of current PARPi, their efficacy in combination with other treatments, and the design of novel inhibitors.

Bob Varelas, PhD, associate professor of biochemistry, will collaborate with Stefano Monti, PhD, associate professor of medicine and biostatistics, to define and understand tumor-stromal signaling networks in triple negative breast cancer. The study will use knowledge gained from network structure analyses of high-dimensional data obtained from human breast cancers to determine how stromal-epithelial signaling hubs influence cell plasticity and aggressive phenotypes using in vivo and ex vivo tumor models to identify vulnerable targets for therapeutic translation.

Daniel Dempsey, PhD, assistant professor of dermatology, will collaborate with William Fairfield Warren Distinguished Professor of Biochemistry Catherine Costello, PhD, and Associate Professor of Pathology & Laboratory Medicine and Ophthalmology Nader Rahimi, PhD, to develop new chemical biology tools to dissect the role of protein modifications in promoting breast cancer to precisely quantitate abnormally modified proteins and define a mechanistic purpose for these changes. Unraveling these mechanisms will identify new vulnerabilities that may be exploited with novel therapeutics to treat patients with breast cancer.

Jingyi Zhao, Ph.D (Garcia-Marcos Lab) awarded 2022 Dahod International Scholar

March 31st, 2022in Departmental News, MGM lab

Congratulations to Jingyi Zhao, Ph.D. (Garcia-Marcos Lab) who was awarded 2022 Dahod International Scholar.

Jingyi, a postdoc in Dr. Mikel Garcia-Marcos’ laboratory, will characterize a small molecule inhibitor of a novel signaling mechanism that promotes breast cancer metastasis. He has identified a promising candidate molecule, named IGGi-11, that disrupts a protein signaling complex specifically present in metastatic cancer cells. He intends to further confirm the specificity of this molecule in preventing cancer cell invasiveness without overt cytotoxic effects in normal cells, and to work towards developing analog compounds with improved properties in preclinical breast cancer models.

New Publication – Researchers Identify Novel PARP-like Enzyme in Mitochondria

The Perissi Lab in collaboration with the Emili Lab has a new publication that came out on February 14th in  the Journal of Cell Biology (JCB) "Neuralized-like protein 4 (NEURL4) mediates ADP-ribosylation of mitochondrial proteins"


For the first time, BUSM researchers have identified an ADP-ribosyltransferase enzyme that is active in the mitochondria (the organelle that generate most of the chemical energy needed to power biochemical reactions in cells) and characterized its activity. ADP-ribosyltransferases are enzymes that play a role in the modification of other proteins. The activity of this new mitochondrial enzyme, called NEURL4, is similar to that of PARP1, a nuclear enzyme well studied for its critical role in DNA damage repair and regulation of gene expression.

To characterize the enzymatic activity of NEURL4, the team led by first and co-corresponding author Maria Dafne Cardamone, PhD, former research assistant professor of biochemistry, first performed in-vitro enzymatic assays. Then they generated a cell line in which NEURL4 was deleted using a gene editing system. From there they used mass spectrometry to compare the modifications on mitochondrial proteins in wild-type (“normal”) versus cells without NEURL4.

According to the researchers this approach led them to identify a number of mitochondrial proteins as targets of NEURL4, including mitochondrial LIG3, a protein involved in the repair of damaged mitochondrial DNA and confirmed that NEURL4 activity is required for the maintenance of mitochondrial DNA (mtDNA) integrity.

While this study does not have any direct implication for clinical treatments, the team says it represents an important step in understanding how cells maintain homeostasis and respond to oxidative stress. “While this will not directly improve people’s quality of life, we hope it will provide fertile grounds for new translational applications for the treatment of diseases with a mitochondrial component, such as cancer, diabetes, age-related neurodegenerative disorders and rare mitochondrial diseases” said co-corresponding author Valentina Perissi, PhD, associate professor of biochemistry and co-director of the Boston Nutrition Obesity Research Center at BUSM.

The researchers believe future studies investigating how NEURL4-mediated modifications of specific mitochondrial proteins affect mitochondrial functions could lead to the identification of novel regulatory strategies to target for therapeutic purposes. A better understanding of NEURL4 biology may also prove relevant for the treatment of male infertility. Mitochondrial DNA deletions are linked with reduced sperm mobility and infertility in both mice and humans and this research indicates that reduced NEURL4 expression in mice is associated with increased mtDNA deletions and markers of male infertility, such as reduced sperm count and increased sperm clumping.

Andrew Emili, PhD, and Julian Kwan, PhD, from the BU Center for Network Systems Biology (CNSB) collaborated on this research.

Cathy Costello receives 2022 Wing Tat Lee Award

March 9th, 2022in Departmental News, Research News

Congratulations to Cathy Costello who was one of six recipients of the 2022 Wing Tat Lee awards, funded to establish cooperative research programs between BUSM and Chinese universities (with a preference for Hong Kong).

Dr. Costello will use advanced analytical methods to collaborate with Huilin Li, PhD, and Yang Mao, PhD, both professors of pharmacy at Sun Yat-Sen University, Guangzhou to, (1) investigate how variations in the amino acid sequences or in post-translational modifications of key proteins affect the efficiency of entry into host cells for variants of the SARS-CoV-2 virus and (2) determine how changes in the structure of a cell surface receptor may alter the course of chronic kidney disease.

Nelson Lau receives 2022 Wing Tat Lee award

Congratulations to Nelson Lau who was one of six recipients of the 2022 Wing Tat Lee awards, funded to establish cooperative research programs between BUSM and Chinese universities (with a preference for Hong Kong).

Dr. Lau's lab will collaborate with Dr. Feifei Yin, associate professor of biology at the Hainan Medical University to characterize virus small RNAs in mosquitoes and ticks from Southern China. This collaboration will build a new BUSM Tick Small RNA Genomics resource to complement the Mosquito Small RNA Genomics resource that the Lau lab has built in collaboration with NEIDL investigators.

New Publication in Molecular & Cellular Proteomics from the Zaia Lab

The Zaia Lab, in collaboration with Prof. Joanna Phillips of the Dept. of Nerological Surgery at the University of California San Francisco, has a new publication out in Molecular & Cellular Proteomics, "In-depth matrisome and glycoproteomic analysis of human brain glioblastoma versus control tissue."

Glioblastoma (GBM) is the most common and malignant primary brain tumor. The extracellular matrix (ECM), also known as the matrisome, helps determine glioma invasion, adhesion, and growth. Little attention, however, has been paid to glycosylation of the ECM components that constitute the majority of glycosylated protein mass and presumed biological properties. To acquire a comprehensive understanding of the biological functions of the matrisome and its components, including proteoglycans and glycosaminoglycans (GAGs), in GBM tumorigenesis, and to identify potential biomarker candidates, we studied the alterations of GAGs, including heparan sulfate (HS) and chondroitin sulfate (CS), the core proteins of proteoglycans, and other glycosylated matrisomal proteins in GBM subtypes vs. control human brain tissue samples. We scrutinized the proteomics data to acquire in-depth site-specific glycoproteomic profiles of the GBM subtypes that will assist in identifying specific glycosylation changes in GBM. We observed an increase in CS 6-O sulfation and a decrease in HS 6-O sulfation, accompanied by an increase in unsulfated CS and HS disaccharides in GBM vs. control samples. Several core matrisome proteins, including proteoglycans (decorin, biglycan, agrin, prolargin, glypican-1, CSPG4), tenascin, fibronectin, hyaluronan link protein 1 and 2, laminins, and collagens, were differentially regulated in GBM vs. controls.

Interestingly, a higher degree of collagen hydroxyprolination was also observed for GBM vs. controls. Further, two proteoglycans, CSPG4, and agrin were significantly lower, about 6–fold for IDH-mutant, compared to the WT GBM samples. Differential regulation of O-glycopeptides for proteoglycans, including brevican, neurocan, and versican, was observed for GBM subtypes vs. controls. Moreover, an increase in levels of glycosyltransferase and glycosidase enzymes was observed for GBM when compared to control samples. We also report distinct protein, peptide, and glycopeptide features for GBM subtypes comparisons. Taken together, our study informs understanding of the alterations to key matrisomal molecules that occur during GBM development.

Corresponding author- Prof. Joseph Zaia, Dept. of Biochemistry, Center for Biomedical Mass Spectrometry, Boston University.

Collaborator- Prof. Joanna Phillips, Dept. of Neurological Surgery, Brain Tumor Center, Helen Diller Family Cancer Research Center, University of California San Francisco, Division of Neuropathology, Department of Pathology, University of California San Francisco.