Friday, August 12, 2016

Week 8

During this last week, I was able to complete my primary research project for the summer, which was to elucidate the genetic basis for resistance to a novel proteasome inhibitor compound in plasmodium falciparum parasites.  Through sequencing of isolated proteasome beta subunit genes, I was able to identify several point mutations in resistant parasite strains that may be responsible for altering the conformational state of the proteasome and thus prevent the proteasome inhibitor from binding.  The next step will be to use CRISPR to induce the identified point mutations in wild type parasite strains and subsequently assessing for the induction of resistance.  Ultimately, knowledge accrued from these studies will facilitate the development of next generation anti-malarial compounds, for which there is a pressing need as current drugs such as artemisinin are becoming less and less effective. 

I also started a mini-project my last week which involved mimicking the mechanical filtration of the spleen in vitro using a matrix of metallic microspheres.  While normal red blood cells are highly deformable, red blood cells infected with plasmodium falciparum decrease in deformability as parasites mature.  This change is believed to be caused by interactions between parasite secreted proteins and the cellular cytoskeleton.  In vivo, the inter-endothelial slits of the spleen trap red blood cells with low deformability, which is the mechanism by which senescent red blood cells are removed from circulation.  This mechanism can be recapitulated in vitro using a matrix of microspheres of sizes 5-25 microns.  Red blood cells flowing through the matrix are forced to undergo dumbbell shaped deformations in the inter-sphere spaces, which is the same type of deformation that occurs during splenic filtration.  In this manner, normal red blood cells can pass through the matrix while red blood cells filled with late stage parasites have a high probability of being retained.  This filtration technique can be used as an alternative to sorbitol-based parasite stage synchronization and can also be used to study other hemolytic diseases such as babesia.  Preliminary experiments conducted using the set-up shown below showed that the microsphere matrix does retain a significant amount of late stage parasite containing red blood cells.  This was a good starting point and Dr. Kirkman’s group will continue to improve and optimize the process.

Filtration set-up

Metallic microsphere layer on pipette filter

Filtration in action

Overall, my immersion term has been an amazing experience and I had a blast spending the summer in New York City.  It was great having the opportunity to interact with clinicians, residents, and fellows and also just being able to enjoy activities the city has to offer during my downtime.  I was able to pick up some molecular biology knowledge through my research and the clinical shadowing portion has granted me extensive insight into how infectious disease care is implemented when an advanced medical infrastructure is available.  Hopefully, I’ll be able to use this knowledge to brainstorm clever ways to bring about equivalent levels of care in low-resource settings for my PhD work.    

Sunday, August 7, 2016

Week 8: New York, New York

Bittersweet is the perfect oxymoron to describe the end of the immersion term. These past weeks have been nothing short of incredible. I strongly believe I was able to meet my goals of better understanding the process of care of cancer patients, particularly lymphoma patients, and of creating a more clinically translational aspect of my PhD project. However, it still feels like I have so much more to learn.

In my final week, I sought to maximize both my clinical hours and produced data. In the clinic, I was able to go into the OR and see an IORT - intraoperative radiation therapy- procedure on a patient receiving a lumpectomy. Through this procedure, after the tumor is removed following the usual lumpectomy procedure, the radiation probe is inserted to deliver radiation to the previous tumor site in hopes of killing microscopic cancerous remains. This intraoperative delivery mirrors the purpose of external beam radiation, which I have witnessed through my past few weeks in the radiation oncology department. With similar purposes and efficacy, IORT can be preferred by patients to prevent skin damage and for the simple matter of convenience. The daily struggle of a cancer patient to simply receive patient, as is the case for external radiation, is often overlooked for the sake of the final diagnosis. Through IORT, a patient is able to receive the best of both worlds - health and convenience. For further information,  please follow this link to watch a video of the procedure. 

In the lab, I finished producing data regarding the growth capacity and differential drug response for the vitally infected and non-infected DLBCL and BL organoids in the context of various integrin ligands. Although the analysis of the data is ongoing, I'm thrilled to report that the project will be continued as a collaboration. Extracting lymphocytes from tonsils also proves to be the second project that will be continued as a collaboration.

Overall, this past week serves as a microcosm of the entire immersion term. It has been a whirlwind of clinical perspective and immediately translating what I learned into the lab. Set against the backdrop of the city that never sleeps, the immersion program was the fast-paced, jumpstart I needed to further motivate me to move forward in my research and to help me understand that my long-term goal of translating my research to the clinic can come sooner than later. 

Friday, August 5, 2016

Week 7 and 8: This is the End, Beautiful Friend

These weeks have been a grind of arranging for patient urine samples, processing them into single cell suspensions, and then assessing cell concentration and viability in the hopes of meeting the quality control conditions for Drop-seq processing. The high sample to sample variability has made this quite challenging, but I was finally able to submit a sample. It remains to be seen if the cDNA library generated meets QC for sequencing.

I was also able to work with a graduate student who set up the Drop-seq system for the genomics facility and learn some of the subtleties in the protocol. This was incredibly beneficial for me as I finish setting up my own Drop-seq in my lab.

Unfortunately, I ended up not observing an actual transplantation surgery, but this is probably for the best as the last time I was in an operating room I ended up passing out. My other experiences working in the research lab, shadowing in the clinic, sitting in on consults and grand rounds, and observing inpatient rounds have made this clinical immersion more than worthwhile.

Until next time, New York.

Tuesday, August 2, 2016

Coming Back to reality!

It is time to go back to Ithaca and return to our original research and environment. Although it feels good to go back home and retake the routine, it is also hard to leave this place that was full of new experiences, learning, and a lot of fun. During my last week in NYC, I concentrated my last days on doing final research about the two approved HIFU technologies to base my report in a formal review and comparison for both of the methods. Since the technology is fairly new (not approved until 2015), there is not enough credible research to follow a formal publishable review, but it is fair enough to produce a good paper. I attended the last board meeting in which I learned uncountable material and a lot of interesting people working with cancer too but from a very different direction. I am so grateful to have the opportunity to live this experience and to work with Dr. Hu in such an amazing field.

On the other side, I also tried to enjoy my last days at NYC. I finally visited the 9/11 memorial and museum which was on my list since the beginning and was one of the couple places I had left to visit. I visited high line, and finally attended a Broadway show. Then, with all of these experiences, I felt like I got everything I wanted from NYC and I will miss this city a lot!!. Mentors/ students final dinner was wonderful, we had such a good time meeting the mentors and sharing our summer experiences. It was such a great end for this excellent experience!

Sunday, July 31, 2016

Final week: Radiology fun and bittersweet goodbye to NYC

Monday: Dr. Prince today gave a very informative lecture about diagnostic radiology. Before the lecture, I was never really interested in radiology. Even though I took a couple classes in image processing that handled medical images to help diagnostics, it was never something interesting to me. In this lecture though, Dr. Prince introduced diagnostic radiology in a case-by-case basis. He asked us to identify the type of images and the body parts shown in the image. Through this process, certain characteristics were drilled in our mind that I don’t think I would forget again. For example, it was confusing between CT images and MRI for most of us but Dr. Prince stated that CT images were mostly lateral images but MRI could be taken from any directional plane. From first glance, a lot of the images appeared to be quite normal, but with Dr. Prince’s guidance, most of us were able to trace the structures of body and eventually identify the abnormality shown in the image and give the correct diagnostics.

One very interesting case I remembered were an MRI image of a pregnant woman. This was the first time I saw an MRI image of pregnant woman and I never knew they allowed radioactive imaging for pregnant woman since everyone was paranoid about the defects of babies that can result from radioactive materials. As far as I knew, I only heard ultrasound that was used during pregnancy. Dr. Prince told us MRI would only be used when there were some significant concerning features they saw in ultrasound images. In this image, the baby can be clearly seen with the head upside-down and placenta attached to the uterus. The image looked perfectly normal at first, but with Dr. Prince’s guidance, we gradually noticed there were some fatty-like material close to the baby’s neck. At first glance, it almost looked at a separate brain, which caused concerns among us since we thought it was an under-developed or defected twin sibling of the baby we already saw. However, Dr. Prince informed us that the condition was cystic hygroma that usually was caused by genetic defects or alcohol/drug use during pregnancy. The size of the cyst was almost same as the size of the baby’s head and was really concerning. Nonetheless, after a little researching on the internet later, I found out that the condition is usually treatable either by surgical removal or chemotherapy after the baby is born. However, the other case of pregnant woman was not so lucky.  The woman had twins but one had a missing placenta and the other had encephaloceles (had brain growing outside of the skull). Dr. Prince said the woman decided to terminate pregnancy and lose both children and they would not be able to survive even though she chose to continue. 

Side note: also after seeing the leakage of breast implant from an MRI image, I think I would never guess a breast implant in my life even though it’s absolutely safe. The image was so bright due to the silicone from the implant and no blood vessel and normal breast tissue could be seen. 

At the end this comes to the end of summer immersion. During this summer, I had the chance to observe in the operating room and ICU talking to patients who were trying to fight the disease; I also got the chance to experience the very border between life and death in the pathology meetings. All of those were something I couldn't expect as a normal scientist and only in the lab. I was surprised and happy to know that there are people thrilled to know about my research and how it could change the life of other patients like them. I really thanked the doctors and residents who were willing to teach and explain to me the anatomy and pathology. I also really thanked those patients who were willing to present themselves as subjects for us to get better understanding of the diseases. Now I m heading back to my lab in ithaca but I will never forget this experience and it will continue to be my encouragement and motivation to make my research meaningful to the biomedical world. 

Saturday, July 30, 2016

Immersion Week 8: One Last Hurrah (Surgical Images Below)

Summary: Finished my time in immersion in neurological surgery and interventional radiology.

I started my week on a positive note and after 4 weeks I was able to finally access OLEA and the PACS system and was able to actually look up patient MRI data. Though, because of the wait, I was only able to investigate volumetric changes in a couple patients. So, I was unable to confidently identify any potential cues for glio-progression, but I still enjoyed the experience.

Next, I was able to observe Dr. Souweidane  in neurological surgery and see the removal of two cysts from two different patients using two different methods. The first patient was an older gentleman that reported losing the capability of doing or remembering simple tasks, but didn’t show signs for stroke. So after MRI was conducted it was determined that the gentleman had a large congenital cyst that had begun to grow and press on to different parts of the brain. To remove the cyst, Dr. Souweidane used guided endoscopy to successfully remove the cyst. The second patient was a young girl who had reported that she was having severe migraines and so an MRI was conducted and it was discovered that the child had an unrelated pineal cyst that was most likely benign, but could be an issue later in life and even cause sudden death. So the patient’s parents decided it would be beneficial to remove the cyst.  For this operation, the rear skull cap was removed and the cerebellum moved forward so the cyst could be located and removed. I’ve included pictured to show the exposed brain and location of the cyst. Lastly, I spent time in interventional radiology observing Dr. May’s cases. I was able to observe an inferior vena cava filter being placed with the aid of x-ray. I was able to wear the lead vest and observe from inside the surgical suite. 

Exposed cerebellum after lower portion of skull is removed. Top to left.

Exposed cyst next to the pineal gland.

Week 8: The End

Today marks my final entry, and the end to my immersion experience as well as time the end to my time in New York City. Leaving the city and the hospital will be a bitter sweet experience.  I am excited to return to Ithaca and continue my PhD work, but I will miss the people, challenging problems, and clinical work here at New York Presbyterian. This week I focused once again on lab work. First, I finished all remaining experiments and data analysis and second, I made a detailed plan with other members of Dr. Spector's lab on how we would like to continue collaborating and finish the project in the long-term. I truly hope to remain in contact with Dr. Spector and the members, as well as others I have worked with, and continue the work that I begun this summer. Looking back, I was able to make some significant progress on the project this summer and helped the lab overcome so hurdles they faced. The dynamic of engineers working with medical students or clinicians is a unique relationship that I have come to cherish. Overall, the immersion experience has taught me a great deal, and given me important insight to how medical devices, biomaterials, or tissue engineered constructs are actually used in the OR or clinic. This knowledge will surely impact how I approach my own research back in Ithaca. 

The experience as a whole has made our class closer and created some strong relationships at Weill Cornell. The shared experience has shaped us all and given us a great deal of perspective not only in our work, but in the medical field as a whole. At our last dinner, Dr. Wang emphasized once again the importance of always thinking deeper about what you are working in and analytically approaching a problem. All important things to remember as I move forward.