Regenerating the lung: harnessing the untapped potential of AT2 cells

Where are they now – Theonie Anastassiadis

Faculty Spotlight: Will Bailis

Be The Match

GRAthletes in CAMB: Coral Kasden competes at 2019 Pan American Games in Lima, Peru

Greening Our Labs

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November 19, 2019

Runny noses, body aches, and chills – dreaded signs that the flu season is upon us. The cough, however, remains one of the most painful flu symptoms and is a clear indication that the influenza virus has successfully invaded the lungs. Though the lungs provide critical protection from environmental insults, they are also highly susceptible to injury caused by influenza. Fortunately, the lungs have a remarkable ability to regenerate in response to infection and disease. Damage to the lung often results in loss of alveolar type 1 (AT1) cells, which make up the majority of the lung epithelial surface and mediate oxygen and carbon dioxide gas exchange. Regene...

July 12, 2019

Although new cases of colorectal cancer (CRC) are on the decline, CRC is amongst the top four most commonly diagnosed cancers in the United States according to the latest NCI SEER report. Underlying risk factors such as smoking, obesity, and family genetic history can lead to malignant transformation of intestinal epithelial cells. At the molecular level, mutations in the genes APC, LKB1, MLH2, and MYH have been associated with colorectal tumor initiation or progression. However, regulation at the transcriptional-translational interface by RNA-binding proteins (RBPs) has not been well characterized within CRC. To clarify the role of the RBPs LIN28B and IM...

February 19, 2019

Malaria remains one of the world’s most devastating diseases. Campaigns to eradicate transmission have yielded encouraging results in recent years. However, expansion of vector habitats has resulted in substantial increases in disease burden in the Americas, South-East Asia, and Africa, with over 2 million new cases and 445,000 deaths reported in 2016.

While Plasmodium falciparum is responsible for most malaria cases in Africa, Plasmodium vivax is the leading cause of malaria elsewhere in the world, particularly in Southeast Asia and South America. P. vivax is thought to have originated as a human pathogen by zoonoses of ape parasites; the long-standing do...

November 27, 2018

When we consider the future of cancer treatment, chemotherapy pales in comparison to immunotherapy. Unlike chemotherapy, which stops or blocks rapidly growing cells and can lead to adverse side effects, immunotherapy modifies a patient’s own cells to enhance or restore the cancer-fighting ability of the immune system. Immunotherapy has led to a marked improvement in clinical outcomes, but unfortunately only a subset of patients respond positively to this treatment. It is well known that different tumors have diverse genetic and epigenetic alterations that contribute to the range of phenotypes, and ultimately the success of treatment. However, the field la...

August 25, 2018

Stemming from a relatively recent explosion of research, the epigenetic regulation of gene expression is now appreciated as an important biological phenomenon. The prefix “epi-” means above or around in Greek, as epigenetics is defined by the study of DNA modifications that do not change the underlying sequence of the DNA. Importantly, these additions change cellular gene expression to diversify the functionality of cells with the same underlying genetic code.

Chemical modifications to DNA such as methyl groups (mCpG) are dynamically regulated to govern cell fate during development. The family of DNA methyltransferase enzymes, or DNMTs, covalently add mCp...

May 28, 2018

Many of us remember being taught a simplified doctrine on histone modifications: certain marks tend to appear on transcriptionally inactive, condensed heterochromatin, while others characterize active, open euchromatin. In particular, H3K27me3 tends to mark facultative heterochromatin that may be expressed during development, whereas H3K9me3 is associated with constitutive heterochromatin. However, histone modifications do not reliably distinguish between heterochromatin and euchromatin, as numerous studies have shown, and as Justin Becker and colleagues in the Zaret lab demonstrate in their recent publication in Molecular Cell1. They debut a new techniqu...

May 28, 2018

The ability to target abnormal genes by introducing functional copies through gene therapy holds extreme promise for the treatment of human diseases. Since the first human therapeutic gene transfer in 1990, gene therapies have been efficacious in treating diseases like hemophilia and leukemia, and this list is continuously growing. Importantly, gene therapies reflect a shift in modern medicine from the treatment of symptoms to the permanent correction of underlying genetic causes of disease.

As not all diseases are created equal, gene replacement therapies are harder to implement if the genetic mutations resulting in pathologies are unclear. Recent resear...

March 1, 2018

Sensorineural hearing loss (SNHL) is a common sensory deficit, which affects 1 in 500 newborns, and can arise from etiologically diverse structural and functional inner ear abnormalities. The mammalian inner ear is an elegant labyrinth that contains a cochlea, the primary auditory organ, and a vestibular system that maintains body balance. Lateral cochlear duct cells, comprising Reissner’s membrane and the stria vascularis, are critical for production, maintenance and secretion of endolymph, a specialized fluid that supports hair cell function. A recent Developmental Cell paper by Alex Rohacek, a DSRB student from Douglas Epstein’s lab, highlights a compl...

March 1, 2018

The human body has over 200 different cell types, and gene regulation is key to establishing and maintaining cell identity. During mitosis, chromatin condenses and long-range interactions between distal enhancers are lost [1]. As a result, scientists have long believed that transcription during mitosis is silenced, raising the question of how cells reactivate transcription to maintain cell identity. How cell identity is controlled is a fundamental biological question, and understanding this process could also provide insights for cell reprogramming and regenerative medicine.

Addressing how cells maintain identity during mitosis is not a trivial issue, give...

November 28, 2017

Cancer research has seen a steady shift towards ‘tumor microenvironment’ driven hypotheses. Tumor cells exploit their environment to fuel their own growth and metastases. Thus, targeting the crosstalk between the tumor cells, stromal cells and the immune microenvironment has gained new appreciation for cancer therapeutics. 

Paracrine or juxtacrine signaling via soluble chemokines and cytokines are the major known drivers of the crosstalk between the heterotypic cells in a tumor. However, the role of exosomes (extracellular vesicles) as dynamic modulators of intercellular communication has only recently been highlighted. A study published in Cell in July 20...

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