Archive for September, 2019

 

Sep 29 2019

A New Year Begins

by at 12:37 pm

Happy Sunday morning. Harriet and I are on a train bound for Trenton, looking forward to celebrating Rosh Hashanah (Jewish New Year # 5780) with our family. In recent years we have done this in DC, but my dad is now too frail to travel. So, this will be a particularly bittersweet celebration, knowing this is very likely the last one we’ll ever have with him. As I have written before, Rosh Hashanah ushers in the 10 Days of Awe, where we are asked to reflect upon the past year and identify actions or thoughts that have diminished our moral obligations to be good to our fellow men and women, and to make amends through our prayers, thoughts and deeds. This is a time of reckoning, as the metaphorical Gates of Heaven open at sundown and will close in 10 days on Yom Kippur, the Day of Atonement.

I am not especially religious, but do find the moral exercise that commences with Rosh Hashanah to be useful. For example, we recently had a terrible incident in our neighborhood where a tenant in a rented house was harboring a dangerous drug ring led by some of her family members, culminating in a dramatic bust led by a small army of law enforcement officers. The perpetrators are in jail, and will not be permitted to return to that house. The neighborhood, which is very peaceful, has been in an electronic uproar, replete with justifiable concerns for community safety but also a tinge of what can only be described as cultural protectionism.

I completely get it, but am nonetheless troubled by what will happen to the primary tenant, who may be either complicit or a victim in the illegal activity. To me, these events raise a larger moral question: how do we react when a neighbor is treated as an invader, as opposed to a full member of our society? In our urge to protect ourselves, what do we lose by failing to reach out? The Old Testament teaches us, “And when you reap the harvest of your land, you shall not reap your field right up to its edge, nor shall you gather the gleanings after your harvest. You shall leave them for the poor and for the sojourner” (Leviticus 23:22).

Are we living up to this revered moral guidance? Our neighborhood issue is, in this context, a metaphor for the larger issues of immigration and tolerance that are at the ugly center of our nation’s political discourse. I fear that there is plenty of blame to go around. All people of conscience decry intolerance, xenophobia and bigotry in all its forms. But, as the famous boxer and philosopher Mike Tyson once noted, “Everyone has a plan until they get punched in the mouth.”

It’s easy to be a liberal with progressive social views at a cocktail party, watching a play at the Arena Stage or on the Saturday morning soccer field. But those beliefs are sorely tested (a punch in the mouth, if you will) when rose-tinted ideology confronts gritty reality. How we respond says a lot about who we are.

I do not pretend to have the answer for how to best address the age-old tensions between protectionism and potentially risky generosity. My best guess is that each situation requires careful thought that fully balances these conflicting impulses. My neighbors chose to protect our communal safety, and that was the proper call in this situation. However, I hope that all of us consider what it means to be truly inclusive, and always remember that the ancient recommendations to leave a bit of the field unharvested so that all may eat is as true now as it was in antiquity.

Whether or not you celebrate this holiday, today begins the rest of our lives, and we have the renewed opportunity to do well and do good. L’Shanah Tovah (Happy New Year)!

Lou

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Sep 22 2019

Showing Up

by at 12:05 pm

From time to time it is a good idea for me to be reminded of the importance of the work we do. We all know it in our heads, and frequently in our hearts, but ah, when it penetrates into our very marrow, that’s when it really resonates. I see patients for many reasons, not the least of which is that the challenges faced by cancer patients remain my personal North Star. However, the process of patient care is just that – a practice that requires I be empathic, while retaining a thin, translucent layer of emotional distance to assure my professional judgment is not confounded by the unbearably sad challenges faced by my patients. But it’s good when something tears a bit of that membrane, even when it is painful. Even when it is not one of my patients.

Our friend Sandy taught with Harriet in the Philadelphia suburbs for years. She and her husband Gerry have been our friends for more than 25 years. They both retired about 15 years ago, and have had a ball, traveling the world (they are up to 50 countries and counting). Sandy is a true force of nature, spreading joy and warmth wherever she goes. We don’t see them as much as we would like, as they moved to Bourne, MA at the base of Cape Cod, near Gerry’s family base. But they are the types of “forever friends” with whom every visit, every call is merely the resumption of a warm, deeply familiar conversation.

We got a different type of call from Sandy about a month ago. She had been diagnosed with stomach cancer, shortly after returning from a wonderful, symptom-free trip to Morocco. Knowing that I am an oncologist, she wanted advice, and I did what I could. Then, the news got worse – she had multiple liver metastases. She does not feel terribly sick, and has started chemotherapy under the care of a wonderful oncologist in Boston. The search is on for clinical trials that might be helpful when they are needed.

How life can change in a flash. One moment, you are wandering around a bazaar in Morocco, enjoying a wonderful vacation, and the next thing you know, you are sitting in a chemotherapy infusion unit, knowing that your treatment is being delivered with palliative intent, and that your anticipated survival is measured in units of months, not years. Sandy is a clear eyed realist about her situation, and her eternally sunny and optimistic nature is now existentially challenged. Hope springs eternal, but this life is not.

What could I do? What could we do? I am exploring clinical trial options for her, but her care team is doing that too. We have no magic wands to wave, but did have one tiny miracle to offer. We showed up.

On Saturday morning, I offered welcoming remarks at a MedStar-sponsored symposium on stomach cancer (cruel irony, that) and sarcoma. I made my excuses, and then Harriet and I decamped to the airport, flew to Boston and drove down to Bourne. We spent four wonderful hours with Sandy and Gerry. We talked about her cancer, life, families and our friendship. Our visit culminated with a lovely meal on an outdoor veranda, watching the sunset over Buzzard’s Bay. Sandy was fatigued (her chemotherapy pump had been discontinued that morning), but was moved and grateful that we had visited. We returned home with our hearts filled with a peculiar mixture of warmth, sadness and fullness. I am so glad we showed up.

We will see Sandy again, and hope that she beats the long odds, if only for a while. In the meantime, and moving forward she remains an inspiration to all who know her and an impetus for my determination to lead innovative cancer research that makes a real difference in this world.

Have a good week.

Lou

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Sep 15 2019

Supercalifragilistic?

by at 9:22 am

I hope you are enjoying the weekend. The last gasp of summer always has a bittersweet quality, but the work at hand is diverting enough to limit the time available to reflect on the changing of the seasons.

I am busy working on a grant application, and have been struggling with how to clinically validate the presence of a particular mechanism of immunotherapy resistance we have identified in my laboratory. We have found that when tumor cells are placed under continuous immune selection pressure by antibodies that mediate a phenomenon known as antibody-dependent cell mediated cytotoxicity (ADCC) they can respond by losing the expression of multiple cell surface molecules, making it impossible for natural killer cells to attach to the cancer cells and destroy them. We call this phenomenon “testudinidosis,” named after turtles that retract their heads and extremities under their shells to avoid predation. I presented this work at a scientific meeting in January and one of the attendees helpfully suggested a way to remember the name and pronounce it correctly. He began to sing a song from the original Mary Poppins movie, “Supercalifragilistic Expialidocious”. Of course, in this case he sang, “Supercalifragilistic Testudinidosis”! Whatever works…

The paper describing these findings was published earlier this year in Cancer Immunology Research. The challenge before us is to determine if this phenomenon actually happens in a clinical context. The selective loss of multiple cell surface molecules is difficult to assess in archival clinical specimens, and fresh tumors obtained before and following immunotherapy are difficult to obtain. The cell surface changes are not accompanied by changes in gene expression. There are some machine learning tools that can be applied to analyze gene expression patterns, but these are somewhat indirect confirmation strategies.

So, I met with our Grand Rounds speaker, James Gulley, on Friday morning and was discussing this challenge with him prior to his excellent Grand Rounds presentation. He suggested we consider isolating exosomes, which can contain enough cell surface membrane-associated proteins to permit analysis by flow cytometry or ELISA. Exosomes can be isolated from the blood, and stored plasma or sera are available from many sources, including our own Survey, Recruitment and BIospecimen Shared Resource (SRBSR). So, we are about to go into a full court press to isolate exosomes from our paired ADCC sensitive/resistant cell lines, and determine if we see similar patterns in their exosomes. Any advice on isolation and analysis of exosomes will be greatly appreciated!

This little vignette illustrates the importance of scientific discourse, engagement with colleagues and broadening our perspectives beyond our individual world views. I had not really thought a lot about exosomes previously, and when James suggested I consider analyzing them it felt like a scientific thunderbolt. It is wonderful to be part of a larger scientific community engaged in understanding profound truths and then leveraging that understanding to make the world a better place. I am a lucky guy.

Have a great week.

Lou

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Sep 08 2019

It’s Been a While….

by at 10:29 pm

It’s been a while. The summer has ended, Labor Day has come and gone and the evenings are beginning to cool down. So much has happened since my last blog; I can’t recall it all. But, a few things stand out and deserve my attention.

First of all, congratulations to Anna Riegel on her appointment as Senior Associate Dean for Biomedical Graduate Education. We all have benefited enormously from Anna’s expert direction of our T Bio graduate training programs, and I am sure she will do a spectacular job. Congratulations as well to Lucile Adams-Campbell for being awarded a prestigious NCORP grant to accelerate clinical trial accruals in our underserved communities, and also for receiving a P20 planning grant for a disparities SPORE in collaboration with Howard University. We have had no shortage of good news on funding of our science this past summer, and this is of course quite promising.

Secondly, congratulations to Mike Atkins and Susan Crockin on the marriage of their daughter Melea this past weekend. We had the privilege of attending the beautiful wedding, and also discovered two wonderful culinary finds in Winchester, VA. Moe’s makes some of the best doughnuts I have ever had, but Steamy’s Cafe makes the best bagels I have had since we moved to the area. They are freshly made, and come either as plain or “everything” (light on the garlic), and are revelations. Plus, they serve our go-to coffee, Corsica, from La Colombe. To be clear, the wedding and attendant celebration were the main attractions of the weekend, but the bagels and doughnuts were nice added touches. Plus, the old town of Winchester is charming and has a few nice Civil War museums if you are in the mood for history.

Speaking of food, the 5th floor of the New Research Building has had the pleasure of dining on burgers and hot dogs on the patio several times this past summer. These get-togethers are organized by one of our unsung heroes, Morse Hendricks. In his 44 years at Georgetown, Morse has always been there to help make things work, supporting our science and enabling our high impact research. It is easy to be swept away by admiration and appreciation of the great work done by our scientific stars, in his own way Morse has been a critically important collaborator in ways small and large. Plus, he makes a pretty fine burger! And, he is not alone. So many of our staff make it possible for Lombardi to strive for greatness. I am grateful to each and every one of them.

Have a great week.

Lou

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