No Cell Sings Alone

An organism is  a chorus. Through an invisible song book its cells follow an omniscient conductor who directs them when to open their mouths and utter a note or a phase;  when the concert concludes, the effects suggest cosmic regulation. Ervin H. Epstein, Jr., MD and Anthony Eugene Oro, MD, PhD investigate how cells work and interact to make normal epithelial organs, such as skin and hair follicles: cells follow molecular conductors, pick up brief nuanced clues, nods, and signals, and they interact with other cells, hormones, and tissues. Sometimes a cell and its progeny follow discordant paths; then cacophony, discomforting rhythms, and disease occur, leaving the chorus a jumbled racket.

Epstein described how  small molecules could be used to correct these aberrant voices and make them rejoin the chorus; alternately, they could be made to abate their shouting and go away completely; or, perhaps, they could be made to wither away and allow other singers to continue on in tune. It can take decades to first identify the squeaky voice in a disease and then to develop an effective and safe means   for silencing it or training it.  Outstanding examples for new and effective treatment for the basal  cell nevus syndrome and the more common basal cell carcinomas of the skin were presented.

Oro discussed how cells could be returned to their youthful, pristine voices and directed to produce clear  tones in harmony with their sister cells.  Dermatologists in the audience perceived how drugs could take the place of surgery or ionizing radiation for treating of skin tumors, and how devastating genetic diseases could be ameliorated with a new set of an individual’s own cells.   Work in progress will focus on preventing resistant clones from growing in tumors undergoing treatment and developing drugs with fewer side effects, or maybe evolving completely new therapeutic modalities.

The final song will be worth the effort.

 

Epstein, EE Jr:  Twacking the Hedgehog

Oro, AE:  Heal Thyself: Using Stem Cell Biology for Skin Disease

 

Presented at the Plenary session of the 75th Annual Meeting of the American Academy of Dermatology, Sunday March 23, 2014, Denver CO, USA.

Sex in Pot City

How do you keep a few  thousand dermatologists in an auditorium at noon on a sunny day in Denver, the legal marijuana capital of America?   SEX.

Sex and dermatologists have a long historical tradition of hanging out together. The  specialty included syphilology from its inception. This audience of international dermatologists heard  David C. Page, MD, director of the Whitehead Institute, professor of biology at the Massachusetts Institute of Technology, and investigator at the Howard Hughes Medical Institute, elucidate how the puny and pathetic-looking Y chromosome could contribute to human health and evolution.  His slides were clear, free of clutter and graphs: just the facts, a “Joe Friday” approach, explaining how sex works — in a manner that was PG-rated and suitable for all ages.

The Big Picture: Page first reassured the XYs in the audience that he is sure there will always be a human Y chromosome, even as the sun begins to dim in our solar system. He is most keen on elucidating mechanisms for  those diseases which differ in incidence between the XXs and the XYs. After the low hanging fruit related to hormones and the immune system is gathered, diseases remain whose marked male predilection requires creative thought to explain, including dilated cardiomyopathy, autoimmune diseases, and autism. The Y chromosome is more than a molecular scrotal sac in the nucleus protecting its one or two critical genes.

Research on  DNA not coding for proteins is becoming more important in many biological systems.  Page did not discuss but is obviously expert in the random inactivation of maternal and paternal X chromosomes in women. Now single cell  analytical methodologies allow many of these cellular questions to be addressed experimentally.

Clinicians and scientists have wondered for millennia about the biological differences between males and females and their relationship to diseases. This ancient conundrum is ripe for the picking.

David C. Page, MD was a guest lecturer at the Plenary Session of the American Academy of Dermatology‘s 72nd annual meeting, March 23, 2014 in Denver, Co, USA.  His talk was entitled ” Rethinking the Pristine X and Rotting Y Chromosomes“.