Cancerous Cells and the Aging Process

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Cancerous Cells and the Aging Process




Guest:  Dr. Lina Obeid – General Internal Medicine/Geriatrics

Host:  Dr. Linda Austin – Psychiatry


Dr. Linda Austin:  I’m Dr. Linda Austin.  I’m interviewing Dr. Lina Obeid who is Professor of Medicine and, I understand, a couple other departments as well.


Dr. Linda Obeid:  Yes.  I also have a secondary appointment in the Department of Biochemistry and Molecular Biology.


Dr. Linda Austin:  Dr. Obeid, your research is in a very interesting area, the intersection of how cells grow, which gets us into cancer, as well as into the aging process.  You told me earlier that you have four different grants going on now.  Scientists often think of their research in trying to answer a question.  If we’re to focus on one aspect or one of those grants, what is the most interesting question to you that you’re grappling with in your research?


Dr. Linda Obeid:  A couple of things.  And maybe a good way of putting it is the interface between cancer and aging.  We know that cancer is primarily a disease of aging, or significantly a disease of aging.  With age, your cells get more injury, more exposure to environmental toxins or other injurious agents.  And they have a choice of becoming what we think of as cancer, that grow indefinitely or mutate, or, if the normal process goes on, cells just become old.  What makes a cell decide to be what we call a senescent cell versus what makes a cell decide to mutate into a cancer cell?

Some of the pathways that we study are at the cusp of that decision.  So, we try to tease out how that happens.  What are the targets of some of these molecules that we study, and how do they make the decision to go one way or the other?


Dr. Linda Austin:  Now, at a certain point in its life, does a cell have to make one decision or the other?  Is there a third choice? 


Dr. Linda Obeid:  Most normal human cells are regenerating all the time and will regenerate from a stem cell into a normal cell.  Now, some tissues regenerate more than others.  Some tissues cannot regenerate at all, for example, brain or neuronal tissue cannot generate at all.  But skin tissue, gastroenteric tissue, for example, intestinal wall, these cells are regenerating at a very fast pace.  So, in general, cells will want to differentiate into a normal cell.  But if they see chronic injury from environmental stresses or toxins, or genetic aberrations, there are a host of underlying pathologies that would lead a cell to take one decision versus the other.


In general, the normal response would be for a cell, if it detects something’s wrong, to undergo ptosis, or self-killing.  A cell will undergo that under some injurious circumstance or, potentially, could become cancerous and grow indefinitely if it didn’t have these checks in place.  And in some cases cells cannot grow, cannot do either one of the above.  They just sit there and become old.  We call them senescent cells and tissues. 


Now, this is a controversial question.  Are there actually senescent cells and tissues?  We’re not sure.  Aging may be sometimes more a fragility of some cells such that they’re unable to regenerate as well, but they don’t have to go on to become cancer.  It’s not very well understood whether, actually, our tissues have senescent cells or not.  It’s one thing we’re trying to understand, aging versus cancer, versus normal processes.  And that’s why stem cells become very interesting, because they can become one or the other.


Dr. Linda Austin:  If there were one scientific question that you could answer in your career, write that paper, do that research that answers that question, what would it be?


Dr. Lina Obeid:  Cancer is very important to me.  I would really like to understand what makes certain cancers.  Now, the thing about cancer, as you study it, you start to see that each cancer is different.  Not all cancers have the same underlying pathology, but there are some common threads in cancers.  And those are deletions or aberrations in certain genes that we know will lead to cancer.  So, there are a few of these that are very common among many cancers.  For example, mutations in a b53 pathway or mutations in the ras-oncogenic pathway will lead to cancer. 


So, these are some of the cancers I’m really interested in finding, to understand these genetic mutations and to fix them.  So, the pathway we work on is a lipid pathway.  Lipids form the cell membranes.  People thought they were just the room that the cell lives in, or that some of the intracellular components lived in.  Lipids, fatty substances, are impermeable to water so they hold compartments.  But some of the research we’ve done has led us to see that these membranes also have a function whereby they’re metabolized in such a way that they can send messages across cells, within cells and from cell to cell.  And these lipids seem to mediate a lot of underlying pathologies in cells, for example, something happens with DNA damage, the lipids can detect that by some indirect mechanism and give a signal.  So, some of these things are what I’m interested in solving and maybe preventing.


Dr. Linda Austin:  So now, in you lab, is this work done in tissue culture, in petri dishes?  If I were to walk into your lab, what would I see?


Dr. Lina Obeid:  It’s very interesting.  Even though I’m a clinician, I started my career in very basic molecular studies and went into more tissue culture models of disease.  And, now, we’re doing a lot of animal models.  As the sciences progressed, we have been able to identify the DNA of many genes, clone these genes and, with the advent of the genomic sequence that has become available, we’re able to identify those genes, pull them out, and now we can take mice embryonic cells and knock this gene out and make a mouse model that lacks this gene.  And if that mouse survives, we can study the function of that gene.  So, we’ve gone from molecular to cellular to animal studies now.  So, you can see all of the above in my lab.


Dr. Linda Austin:  Dr. Obeid, thank you so much for talking with us today.


Dr. Lina Obeid:  Thank you.  It was a pleasure.


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