The Lesser Known Vessels in the Heart

The fact needs no reiteration that cardiovascular disease (CVD) remains the leading cause of mortality worldwide – root cause being the obstruction in the coronary arteries, which hinders the blood supply to heart. If this obstruction in the coronary arteries arises in a neonatal rodents or newborn babies, their heart can regenerate with its intrinsic capacity and recover from the disease. However, adults are devoid of such advantage. A newly published study in Cell1 unraveled the mechanism of how the neonatal heart can regenerate while adult cannot. One of the aspects in neonate heart is the development of collateral arteries following the heart injury. While not much is known about these small arteries, they play a significant role in the recovery process by bridging the two conventional arteries or unobstructed areas of a single artery leading to a natural bypass that restores blood flow downstream of an obstruction (Figure 1).

Diagram showing the collateral arteries forming a bypass to restore blood flow below an obstruction.

Figure 1: Diagram showing the collateral arteries forming a bypass to restore blood flow below an obstruction.

To see the pattern of these collateral arteries in neonatal vs the adult mice, authors of the study performed a left descending artery (LAD) mimicking a myocardial infarction in P2 mice (when the heart can regenerate) vs P7 (non-regenerative phase of the heart). While they observed significant regeneration of collaterals appearing in the watershed area (midline) of the heart in P2 mice, P7 mice were devoid of these features.

Figure 2: Collateral artery development is restricted to neonatal regenerative phase (source: reference 1).

Figure 2: Collateral artery development is restricted to neonatal regenerative phase (source: reference 1).

One thing which dramatically changed in the P2 mice after the injury was the appearance of chemotactic ligand Cxcl12 in the capillary endothelial cells (ECs) which is generally present in arterial ECs in non-injured hearts and plays an important role in guiding coronary EC migration during embryonic development. The necessity of CXCL12 and its receptor CXCR4 in the regeneration process was evident by their deletion from the cells as a result of which cells were unable to form collateral arteries and to recover from the MI injury. The authors in this study made an attempt to explain the model in the following diagram (figure 3).


Figure 3: Induction of capillary CXCL12 attracts CXCR4 expressing artery cells out from arteries and into the watershed, where they subsequently proliferate and reassemble into collateral arteries (source: reference 1)

Figure 3: Induction of capillary CXCL12 attracts CXCR4 expressing artery cells out from arteries and into the watershed, where they subsequently proliferate and reassemble into collateral arteries (source: reference 1)

Now, after learning all these exciting concepts, question comes to my mind, what’s its clinical relevance? Does the activation of CXCL12 can somehow stimulate healing in adult heart where endogenous regeneration is limited? To answer this question, the authors injected exogenous CXCL12 directly into the adult mouse heart at the time of MI and to their surprise one dose of CXCL12 stimulated the collateral development process (Video 1). It was previously known that CXCL12 can decrease the scar size and improve heart function after MI2 but now this study suggested that improvement in the functional credentials could have been contributed by formation of collateral arteries in the adult’s injured heart.

Video 1: Single dose of CXCL12 showed an increase in vessel density in the watershed area of heart after MI (source: reference 1)

Thus, this study provided a novel neonatal regenerative pathway which involves migration of arterial endothelial cells to build collateral arteries which can provide blood flow under conditions of infarction or vascular occlusion and has the potential to be harnessed for adult ischemic heart disease (figure 4).

Figure 4: Formation of unique collateral arteries promotes neonate heart regeneration (source: reference 1)

Figure 4: Formation of unique collateral arteries promotes neonate heart regeneration (source: reference 1)




  1. Das SGoldstone ABWang HFarry JD’Amato GPaulsen MJEskandari AHironaka CEPhansalkar RSharma BRhee SShamskhou EAAgalliu Dde Jesus Perez VWoo YJRed-Horse K. A UniqueCollateralArtery Development Program Promotes Neonatal Heart Regeneration. Cell. 2019 Feb 21;176(5):1128-1142.e18.
  2. Sundararaman SMiller TJPastore JMKiedrowski MAras RPenn MS. Plasmid-based transient human stromal cell-derived factor-1 gene transfer improves cardiac function in chronic heart failure. Gene Ther.2011 Sep;18(9):867-73.







Industry vs. Academia: Which Road To Take?

If you are an early career researcher, this question might have crossed your mind at some point: “What’s the best career choice after finishing my PhD – ‘industry’ or ‘academia?'”

While you will still be called a researcher, the context of work changes when you pick one or the other option. Like myself, who is still contemplating between the options, it is really important to understand the differences between both career choices. It is also very critical to make your decision on basis of your interests, skills, qualifications and personality. I personally make my decisions with a critical eye listing all the pros and cons, which I will be sharing with you.



Work Independence:

Your work responsibilities in an industry are based mostly on supply and demand. Whatever product is in demand, most likely your project will be focused on that specific product development. This can also mean that there will be clear direction of work without you wasting time on things which might be uncertain to work. This can be a best case scenario if your personal project interests align with the company’s. However, in most instances, your work (or broadly speaking, your career) will be controlled by higher authorities.

Whereas in academia, you have a freedom of exploring different horizons. It’s up to you to design and pursue your own project with or without limited direction from senior authority. Your job will be more intellectually adventurous as you will be constantly thinking, reading and exploring new ways to solve a problem.



To some of us, finance plays a big role in deciding our career… but for others, the decision is purely based on what you enjoy doing. Generally speaking, the salaries in industry are 1.5 to 2 times higher compared to academia. While the world is brighter on industry side, you don’t even want to know about how much graduate students and postdocs earn.

Late 20’s and early 30’s is typically the time when you want to buy a house or start a family, but these things just seem far-fetched in your early academic career years. On the positive side, if the promotion or bonuses sound unreal in academics, maintaining employee satisfaction is bit accessible. This can be a hard earned task in industry given the cost of bringing on a new hire is so high.


Work responsibilities:

Most research jobs in the industry are standardized and structured to align with the company’s management. You may have more time to contribute to multiple projects, but the ideas/instructions may be coming from a different team directing which goals are best for company’s progress (and not your personal research interests).

Whereas in academia, as a PI for instance, the scope of your responsibilities would be much wider and entrepreneurial. It surely depends on your size of your institution, but more or less you will find yourself applying for grants, mentoring your students, publishing your research, looking over your finances, and at some places you will be responsible for teaching students, as well. If you obtain tenure, you are pretty much guaranteed a job, which can be a struggle in industry if you unable to reach the goals set for that particular year. Academia also gives you the liberty of finding your own boss, whereas industry doesn’t.



If you are a family person or likes to work at your pace, then academia is the way to go. In most cases, you don’t have to stick to work hours. You are able to make your own work schedule and hence work environment in your lab. You may have grant and manuscript revision deadlines, but they can’t be compared with rigorous quarterly deadlines or monthly reports in an industry.

The pace at which these 2 sectors works is also very contrasting. Where academia is free of short term deadlines and focuses on long-term education and learning goals, industry is fast paced where most of work is done on quick timeline driven by product development goals.


So, if you are asking yourself this big question about which career path to choose, first understand what kind of personality you have and what your life priorities are. It is really important to know your strengths and which place they can be more effectively applied. Also, it is of great importance to be open minded and keep your options open – especially now when industry is collaborating with academia to conduct research, it has become little smoother to transition between the sectors. I hope some of my thoughts would help you choose the right direction.



microRNA – Small RNA, Enormous Powers

If you could peek inside one of the cells in your body, it more or less looks like a factory in which various machines are undergoing different molecular processes. The ultimate goal of this cell machinery is to synthesize a protein. Thus, to produce these complex structures, there are other entities required in the cells known as DNA and RNA.

Double stranded DNA, which holds all the blueprints for the proteins, firstly gets converted into single stranded RNA molecules by the process called transcription and these newly synthesized RNAs are further translated into proteins. In addition to this, there are some negative regulators of the gene expression at the post transcriptional levels known as microRNA (miRNA).

As the name suggests, miRNAs are small 21–25 nucleotide, single stranded, endogenously expressed RNAs which do not code into proteins. These miRNAs are transcribed from DNA in the nucleus and are processed with the help of enzymes (RNA polymerase II and Drosha) and exits the nucleus upon which its further undergoes cleavage with enzyme called dicer. Once matured, miRNA enters the RNA induced silencing complex (RISC) which guides it to target mRNA sites, where it is able to repress protein production by destabilizing the mRNA and induce translational silencing (Figure 1). miRNAs are fine tuners of the gene expression and have been reported to be critical regulators of cardiomyocyte (CM) differentiation, proliferation and other cellular processes during embryogenesis through the adult life.


Figure 1: miRNA synthesis and processing in the cell (image taken from reference 1)

So, let’s just talk about role of these powerful miRNA in cardiac regeneration. Many non-mammalian vertebrates are capable of complete regeneration of the heart after an injury throughout their life by re-entry of existing CMs into cell cycle and compensating for the loss of contracting cells. However, mammalian hearts are not blessed with such advantage and CMs undergo nuclear division without cytokines leaving most of the cells binucleated. Under normal conditions, adult mammalian CMs renew to replace the cardiomyocytes that undergo apoptosis at a rate of 0.5–1% a year, while this number is insufficient to replace 1 billion CMs lost during myocardial infarction. Thus, the most feasible strategy to overcome this loss is to coax the preexisting CMs into proliferation.

In the heart, miRNAs have been found to be closely intertwined with cardiac signaling and transcriptional pathways to regulate CM proliferation. High throughput miRNA screening has provided new insights in the role of miRNA in sending the CM back in cell cycle and thus, providing an opportunity of innovative therapies of cardiac repair.

In a recent study, Huang and colleagues reported miRNA-128 upregulation in CMs during the postnatal switch from proliferation to terminal differentiation and hence its deletion extends proliferation of postnatal CMs2. Other experiments conducted in mice indicated the increase in mRNA of 2 targets involved in CM growth and proliferation upon deletion of miRNA -133 family members mi-133a-1/miR-133a-2. miRNA-15 family presents another example for role of miRNA in CM proliferation. miR-195 (member of miR-15 family) was found to be a vital regulator of cell cycle genes and its up regulation inhibits cell cycle progression and induces mitosis arrest postnatally.

Further, studies in zebrafish model demonstrated the downregulation of miR-99 and Let-7a/c miRNA family during of regeneration of amputated ventricular apex while over expression of their target proteins resulted in CM differentiation and proliferation. On the contrary, few miRNA have been identified whose induction have led to remarkable stimulation of CM proliferation and cardiac repair. A study conducted on CMs from adult rats received a lot of appreciation when they showed miR-590 and miR-199a delivery to the cells induced their reentry into cell cycle postnatally3.

The studies mentioned above have shown exciting results which can lead to long-lasting and potent effects of miRNA in cardiac repair especially by the stimulation of post-natal CM proliferation (Figure 2). Despite the successful results obtained in vitro studies, miRNA delivery systems for transporting the molecules to the heart have yet to be optimized.

Figure 2: microRNAs in cardiac regeneration

While miRNA is an excellent therapeutic target because of its ability to target multiple genes in a single disease, further works needs to be done to improve its local targeting and reduce cost and toxicity in order to make it possible to use this excellent system to promote CM proliferation in pre-clinical or in clinical settings.



  1. Beezhold KJ, Castranova V, et al. Microprocessor of microRNAs: regulation and potential for therapeutic intervention. Mol cancer. 2010;9:134
  2. Huang W, Feng Y, et al. Loss of microRNA-128 promotes cardiomyocyte proliferation and heart regeneration. Nat Commun 2018;9:700. 
  3. Katz MGFargnoli AS, et al. The role of microRNAs in cardiac development and regenerative capacity. Am J Physiol Heart Circ Physiol.2016;310(5):H528-41.



Diabetes Makes Heart Disease Worse

Global awareness has made us cognizant that people with diabetes are susceptible to various disorders involving eye, kidney or nervous system and blood circulation affecting the limbs in the long run. Along these lines, type 2 diabetic patients are more likely to develop heart disease and have a greater incidence of heart attack. According to American Heart Association (AHA), diabetes is one of the major contributing factors for cardiovascular disease and accounts for at least 68 percent of diabetic population of age 65 or older to die from some form of heart disease.

Diabetic heart disease (DHD) is a broader term used to explain heart problems in patients who have diabetes. DHD may include conditions like coronary heart disease, where plaque accumulating in your arteries reduces the blood flow to the heart eventually leading to heart failure, a condition where your heart cannot pump enough blood to meet your body’s requirements. Another consequence of diabetes can be diabetic cardiomyopathy where the damage is extended to the structure and function of the heart. Patients with diabetic cardiomyopathy are more predisposed to develop irregular heartbeat disorders called arrhythmias.

Arrhythmias are conditions in which there is a problem with the rate or rhythm of your heartbeat. It is observed when the electrical signals to the heart that coordinate heartbeats do not function properly. This leads to increase in heart rate (basal rate of more than 100bpm), a condition called trachycardia or decrease in heart rate (basal rate less than 60bpm), called bradycardia. The detailed illustration of these conditions can be found at AHA website. While these conditions can have serious complications in patients, the condition becomes far worse in patients with DHD.

Under normal conditions, mitochondrias which are the energy sources of the cell, give rise to dangerous chemicals known as reactive oxygen species (ROS), byproducts of aerobic metabolism. Oxidative stress occurs when there is excessive production of ROS and if these chemicals are not removed, they possess damage to proteins, tissues and genetic material of the heart cells. However, mitochondria have antioxidant defense systems which decrease ROS production. Under pathological conditions such as diabetes, glucose fluctuations far exceed the ROS production than the oxidative defense systems are capable of cleaning and thus the problem becomes far more intense.

At this year’s Scientific Sessions, one of my colleagues presented his work establishing an interesting link between oxidative stress and arrhythmias. His project focused on protein which is a key enabler of ROS- mediated cardiac arrhythmias, known as mitochondrial translator protein (TSPO). TSPO is an outer mitochondrial membrane protein, previously described as peripheral benzodiazepine receptor, a secondary binding site for diazepam. It’s primarily associated with cholesterol transport to inside the cell, while the group explains its potential role in mitochondrial instability during arrhythmias by mechanism, where excess ROS generated in diabetic patient positively up-regulates its own levels – a process called ROS induced ROS-release (RIRR). Thus, TSPO can be a potential therapeutic target against arrhythmias in diabetic patients. Preliminary data by the group confirmed the increased levels of TPSO in hearts of diabetic rats, which might be responsible for increased propensity of diabetic hearts to arrhythmic events. While TPSO is probably upregulated as compensatory mechanism during type 2 diabetes, its global gene silencing may interfere with essential homeostatic function including cholesterol import and mitochondrial biogenesis. In relation to that, the group is further looking into avenues for targeted and specific TSPO inhibition in the areas affected after heart attack.

Personally, I am not only proud of his work but also hopeful that research studies like his help us to identify potential targets for curing serious conditions like DHD.



Ilkan ZAkar FG. The Mitochondrial Translocator Protein and the Emerging Link Between Oxidative Stress and Arrhythmias in the Diabetic Heart.Front Physiol. 2018;26;9:1518

Ilkan Z, Strauss B, Akar FG. Reversal of TSPO Upregulation in the Diabetic Heart by Chronic TSPO Gene Silencing Causes Metabolic Sink via an Increase in ROMK Expression. Circulation. 2018;138:A16826.




Stem Cell Therapy For Heart Failure- Results From First Clinical Trial

Among the various treatment regimens being investigated, cell therapies have achieved the furthest development in human medicine. With the paucity of donor organs and long-term immunosuppressive treatment, replacement of damaged cells within the cardiac tissue with stem or primary cells have offered hope to treat heart failure. The choice of cell type for this application is assured by its accessibility, the risks it may pose and their application in clinical practice. While many other types of cells are under investigation, pluripotent stem cells (PSCs) derived from the embryos namely embryonic stem cells (ES cells) have shown unique and extraordinary capabilities in regenerative medicine. Nonetheless, due to their highly expandable nature and ability to differentiate into various cell types including tumor cells, these cells were never tested in clinical trials until recently.

A recently published study dictates the outcome of clinical trial implementing the use of human ES cell-derived progenitors in severe heart failure. This study represents the first clinical testing of human ES cells in patient suffering from cardiac disease. The trial recruited 6 patients from 2013 to 2016 with diagnosis of severe left ventricular systolic dysfunction (left ventricular ejection fraction ≤ 35%, which is characterized as severe class III ischemic heart failure according to New York Heart Association (NYHA). After taking all safety measures into considerations, the group was granted approval for delivering ES cells in vivo by French regulatory agency after 10 years of encouraging preclinical and translational results.  The first clinical case report of this trial was initially submitted in European heart journal in 2015 which presented the details of their approach and 3 month follow up results from a single patient involved in the clinical trial.

In the presented trial, ES cells were obtained from human I6 line and expanded to desired number of cells required for transplantation in a clinical grade environment. As the heart is derived from the mesoderm, commitment of ES cells towards mesodermal lineage was induced by bone morphogenic protein BMP-2 while reduction of fibroblasts growth was maintained by its inhibitor SU-5402. The purified population of stem cells was sorted by expression of stage specific embryonic antigen (SSEA-1, marker for loss of pluripotentcy) co-expressed with cardiac transcription factor Isl-1. These cells were incorporated into fibrin patch and delivered into pocket created between pericardium and epicardium at the same time of coronary bypass.

Upon 1 year follow up, authors observed no complications related to the surgery. Patient’s cardiac functional status showed remarkable improvement with LVEF increased by 12% and reduction in LV end diastolic and end systolic volumes owing to integration of the grafted cells into the heart tissue. An internal cardioverter defibrillator neither showed any signs of ventricular arrhythmias, nor were there any tumor like formations in the heart detected by computed tomography (CT) and %uFB02uorine-18 deoxyglucose positron emission tomography (PET) scans performed at 6 months (PET scan) and 12 months (CT scan) post operatively. Also, no immunosuppression related adverse events were evident. Additional analysis confirmed that delivery of the ES cells patch not only revascularized the infarcted area but also significantly improved the wall motion of cell/patch treated segment of the heart.

By demonstrating that human ES cells can be differentiated in clinical grade cardiovascular progenitors, the authors have confirmed the scalability and pluripotentiality of these cells which can be now safely delivered in patients with heart disease. Thus, encouraging results from this study has certainly provided an insight for taking cell-based therapies from bench to bedside.


  1. Menasché P, Vanneaux V, Hagège A, Bel A, Cholley B, Parouchev A, Cacciapuoti I, Al-Daccak R, Benhamouda N, Blons H, Agbulut O, Tosca L, Trouvin JH, Fabreguettes JR, Bellamy V, Charron D, Tartour E, Tachdjian G, Desnos M, Larghero J. Transplantation of Human Embryonic Stem Cell-Derived Cardiovascular Progenitors for Severe Ischemic Left Ventricular Dysfunction. J Am Coll Cardiol. 2018;71(4):429-438.
  2. Menasché P, Vanneaux V, Hagège A, Bel A, Cholley B, Cacciapuoti I, Parouchev A, Benhamouda N, Tachdjian G, Tosca L, Trouvin JH, Fabreguettes JR, Bellamy V, Guillemain R, Suberbielle Boissel C, Tartour E, Desnos M, Larghero J. Human embryonic stem cell-derived cardiac progenitors for severe heart failure treatment: first clinical case report. Eur Heart J. 2015;36(30):2011-7.

Keerat Kaur Headshot
Keerat Kaur is a postdoctoral fellow at Icahn school of Medicine at Mount Sinai in department of cardiology, NY. Her research focuses on reprogramming non-cardiacmyocytes to cardiomyocytes using modified mRNA approach.



Dynamism Of Epigenetics

You may have heard the fascinating term epigenetics in news articles or scientific journals as a miracle panacea for every disease. But wait a second, let me decipher this tough term for you. The literal mean of ‘Epi’ is above and ‘genetics’ is the study of heredity and the variation of inherited characteristics. Thus, epigenetics can be described as the additional information layered on top of the genetic material (DNA) that determines how the information in the genes (made up of DNA) is read by the cells. These epigenetic changes hold the capacity to decide which proteins to be transcribed or not. Take an instance, many of you replicate the recipes that you watch on cooking channel. Some of you would add the same amount of ingredients as suggested but few might just add little less salt or some extra spices. Similarly, your phenotype is the result of switching on and off your 20,000 genes with regards to your milieu, food you eat and the lifestyle choices you make.
Epigenetic changes allow different cells from same individual to behave profoundly different from each other, despite carrying essentially the same DNA sequence. For example, your liver and skin cells are genetically identical, however they don’t necessarily follow the same steps of the instruction manual and become specialized in their own way, process known as cell differentiation. The basis of epigenetics is the covalent chemical modifications of DNA itself or the histones hugging the DNA string. Addition of these chemicals tags like methyl, acetyl, ubiquitin or a phosphoryl group can choose to activate or repress the function of certain genes and these outcomes can be transmitted to daughter cells, although many researchers report that some epigenetic changes are reversible.
Hopefully, by now I have piqued your interest in this field. Let’s take a look at how changes in epigenetics may lead to undesired outcomes. Epimutations cause complex disorders like Prader-Willi syndrome and Angelman syndrome due to errors in genomic imprinting with loss of imprinted (parent-specific) genes that are only expressed from the chromosome of one parent. Considering the more common diseases, epimutations are hatched by various environmental factors resulting in the modulations in the DNA methylation and histone modification patterns as well as altered expression profiles of chromatin-modifying enzymes which turn the healthy cells into malignant phenotype. Most talked game player in the field of cancer is DNA methylation, which if in low levels can cause abnormally increased expression of growth-promoting genes (oncogenes) while its elevated levels reverse the work of protective tumor suppressor genes.
Aforementioned, during embryonic development, commitment of a precursor cell to a more specialized cell occurs in a precise differentiation process, which is driven by a multitude of epigenetic modulations. Chen and Dent (1) summed up the importance of histone methytransferases and deacetylases in post translational modifications required during different stages of cell development and differentiation processes. Mutations in these enzymes have been reported to cause serious disorders including cancers, autoimmune disorders, neurological disorders (Fragile X syndrome, Huntington, Alzheimer, and Parkinson diseases and schizophrenia), making them prime target of researchers in biomedical research and clinical therapy. I have personally contributed to this field by establishing the differentiation of mesenchymal stem cells to cardiac competent cells and also enhancing the numbers of cardiac progenitor cells by employing a histone methytransferase inhibitors in an effort to provide an accessible adult stem cell population for cardiac repair (2,3).
Although science of epigenetics has taken over every laboratory bench space, further research is needed to better understand how epigenetic diseases emanate. Scientific organizations like International Human Epigenome Consortium, are coordinating human epigenomes from different types of normal and disease-related human cell types aiming to determine how the environment and nutrition will modulate epigenetic alterations. Thus, new research data and high-throughput sequencing technologies may help to develop better tools to diagnose patients and provide optimal cell therapies.

1. T. Chen, S.Y.R. Dent. Chromatin modifiers and remodellers: regulators of cellular differentiation. Nat Rev Genet. 2014. 15(2): 93-106.
2. Mezentseva NV,Yang J,Kaur K, Iaffaldano G, Rémond MC, Eisenberg CA, Eisenberg LM.  The histone methyltransferase inhibitor BIX01294 enhances the cardiac potential of bone marrow cells. Stem Cells Dev. 2013;22(4):654-67.
3. Kaur K, Yang J, Edwards JG, Eisenberg CA, Eisenberg LM. G9a histone methyltransferase inhibitor expands adult cardiac progenitor cells without changing their phenotype or differentiation potential. Cell prolif. 2016 Jun;49(3):373-85.

Keerat Kaur Headshot

Keerat Kaur is a postdoctoral fellow at Icahn school of Medicine at Mount Sinai in department of cardiology, NY. Her research focuses on reprogramming non-cardiacmyocytes to cardiomyocytes using modified mRNA approach.



Coming Out From A Burnout!

When I think about an example for burnout, the first thing comes to my mind is the movie ‘Pursuit of Happyness’. In the movie, Will Smith juggles between professional failures, financial instability, and raising his son as single father. Yet, he refuses to give in to despair, works hard to overcome the hurdles and everything falls in place for him towards the climax. That makes me wonder, does it really happen in our everyday life? Do we ever get to maintain a work life balance and get our happily ever after?
While numerous studies have been concluded to analyze and ablate the levels of burnout in physicians and nurses, it is seldom discussed in field of biomedical research. After spending on average of 5 years in PhD, the hopes of settling in our careers swiftly are really high and with the universities and industries becoming more competitive each day, makes it pretty evident that ‘PhD is not enough.’
With degrees in hand, most of us find ourselves in the pool of postdoctoral fellowship with an ambition to launch one’s career. In this postdoctoral world, where fellows are constantly contending against each other, only a handful will fulfill their dream of landing a permanent faculty position. Well, that doesn’t come as easy as it’s said. It requires years and years of tremendous effort in writing grant proposals, publishing research papers and presenting at scientific meetings rewarded with very low wages and no job securities. To add to the pressures, the postdoctoral period is usually a time of life where we are entering the real adulthood where most people start their families and/or buy a house. While these heaps of workload turn us into perfect multitaskers, many of us may develop a feeling of stress for not providing enough time to family or work and accumulation of these feelings bring us one step closer to burnout.

Following diagram depicts the main causes of Burnout in biomedical researchers:

How to deal with this burnout? Well, here are some of my thoughts:
1. Identify the cause– To pit against burnout, the first thing to know is what triggers your stress levels. You can take out time and list the things that cause distress or note the event that made you anxious. It can be your work hours, competitiveness with your colleagues, or over commitment to tasks.
2. Adopting a healthier lifestyle– To combat burnout, it is pivotal point to become physically active. Numerous studies have shown that exercising regularly can reduce stress and prevent the development of a deeper depression. Also, getting enough sleep can replenish your body fuels. Researchers have established that attaining less than 6 hours of sleep per night may lead to impairment of mental function and thus making you more susceptible of making errors.
3. Reassess and prioritize your goals– As a postdoctoral fellow, it is important to define a clear long-term goal to get the most of your training period. However, writing down your targets for a shorter time span (weekly or daily basis) may help to finish one part of a larger project. Ranking your targets for the day and finishing them on priority basis may help in increasing productivity and provide a feeling of accomplishment. As a researcher, you may hit a roadblock with your experiments or writing a grant. However, it is okay to be flexible with your expectations. Don’t think less of yourself if you adopt a plan B. Reevaluate your final goal, think about your strengths and expand your research horizons.
4. Identify the things which make you happy– When burnout seems inevitable, identify the things which bring happiness to your life. It may be spending time with your family, taking a swim or going on an excursion. Use these resources to recharge your batteries and return to work with a positive attitude.
5. Surround yourself with positive people– Last but not the least, it is really important to keep an optimistic approach towards your goals and spend time with like-minded people who may encourage and support you through every step of the way. It is okay to seek advice from a trusted mentor or a senior person in the lab. Listening to positive research experiences of your peers rejuvenates your interest in the field and makes your job fun and exciting.
“You will burn and you will burn out; you will be healed and come back again.”
– Fyodor Dostoyevsky, 

Keerat Kaur Headshot

Keerat Kaur is a postdoctoral fellow at Icahn school of Medicine at Mount Sinai in department of cardiology, NY. Her research focuses on reprogramming non-cardiacmyocytes to cardiomyocytes using modified mRNA approach. 



Finding Panacea For Heart Disease Through Signaling Pathways

After an insult, a series of stress events are activated in the heart leading to heart failure. To prevent processes leading to adverse cardiac remodeling, cardiomyocytes activates gene expression pathways which closely resemble to those observed in fetal cardiac development. One of such cascade activated is Notch signaling pathway which plays a critical role during mammalian cardiac development. Notch is an evolutionarily conserved signaling pathway that is important for multiple cellular processes, including cell fate determination, differentiation, proliferation, apoptosis, and regeneration during embryonic and early postnatal development. Activation of this signaling pathway involves the interaction of membrane bound Notch receptor with Delta-like or/Jagged ligand. Following this interaction, protease complex γ-secretase cleaves the notch intracellular domain (NICD) which translocates to the nucleus and promotes gene expression of hairy and enhancer of split (HES) and hairy transcription factor (HRT) by binding to the protein suppressor RBP-J. This notch transduction system is gradually silenced in the heart after birth but is partly restored in myocardium following injury.

On the contrary, expression of voltage-gated K channels is progressively increased during postnatal development, leading to the acquisition of the mature electrical phenotype.  These outward Kcurrents are critical determinant of the action potential (AP) profile of the cardiomyocytes. Importantly, K channels are reduced after myocardial infarction, an event that is accompanied by reactivation of Notch signaling. At this year’s AHA scientific sessions, I presented my work on hypothesis that NICD transduction system contributes to the electrical remodeling of myocytes of the diseased heart.

Our electrophysiological studies in NICD-GFP transgenic mice showed that activation of NICD presents a prolongation of early repolarization phase of AP which is primarily determined by the outward Kv currents. Upon further investigation, voltage clamp experiments displayed significant decrease in various components of Kv currents in myocytes expressing NICD compared to control. To establish a causative link between notch activation and electrophysiological properties of myocytes under pathological conditions, we induced the myocardial infarction in C57Bl/6 WT mice and perturbed the notch signaling in these mice by using an antagonist of γ-secretase. Isolated cardiomyocytes from these mice prevented the reduction of Kv currents compared to the myocytes from non-treated mice where Kv currents are substantially reduced. Taken together my poster summarized that Notch signaling is an important regulator of the electrical properties of cardiomyocytes under normal and pathological conditions.

Presenting my work at AHA was one of the biggest highlights at the conference. Not only I got the opportunity to share my research with such a large audience, I was elated to receive positive input regarding my work from the experts whose papers I have read. This trip has definitely connected me with greater scientific community and opened doors for potential collaborations. I have returned home feeling energetic and inspired. I can’t wait to be back at AHA 2018.

Keerat Kaur Headshot

Keerat Kaur is a postdoctoral fellow at Icahn school of Medicine at Mount Sinai in department of cardiology, NY. Her research focuses on reprogramming non-cardiacmyocytes to cardiomyocytes using modified mRNA approach.



Entering The Scientific World- As A Woman

As I was entering into the Anaheim downtown area, I was just mesmerized by people walking with red tags around their necks bringing a smile onto my face, giving me a sense that they all belong to the same community as me, the scientific community. There are so many emotions running inside me, contemplating how I am going to make most of out of my next 3 days, rejuvenating to see such young talent around me and inspired to meet renowned researchers in the field of cardiology whose work I have been reading for many years. Scientific meetings are the best platform to foster new ideas, raise awareness and make your acquaintances beyond your geographical scope and there is no better way than AHA meeting. By bringing together basic researchers, scientists, and clinicians, AHA is providing the biggest platform to take the research from bench to bedside.

While everyone was talking research, one thing I was captivated was the acknowledgment that women were granted in this place. When women are constantly fighting about equal rights in workplace and equal wages as men, AHA is recognizing women with various achievement awards and named lectures. My highlight of yesterday was the American Heart Association Woman of Distinction Award for outstanding dedication to heart failure awareness which was presented to Queen Latifah during the opening ceremony. Singer, songwriter Queen Latifah inspired by her mother Rita Owens has contributed significantly in ‘Rise above heart failure’ movement and thus educating the community regarding symptoms and treatments of the condition and providing awareness to lead a healthier lifestyle. I personally being a fan of Queen Latifah’s work was delighted to see her getting honored at such a reputed conference. As a woman myself, one thing which made me swell with pride was that the presenter of the award was another renowned woman entrepreneur Nancy Brown, Chief Executive Officer of the AHA/ASA. AHA is breaking boundaries and constantly fighting against gender disparities between women and men by providing equal opportunities for women at places of work and in their levels of responsibility. In the field of medicine, AHA also recognizes outstanding academic and clinical performance in women cardiology fellows during cardiovascular-related specialty training by providing Women in cardiology excellence trainee awards for excellence. Other than the awards and honors, AHA also nurturing a council on Arteriosclerosis Thrombosis and Vascular Biology (ATVB) Women’s Leadership Committee (WLC) encouraging women’s involvement in science by providing visibility and engagement of women in ATVB activities, meetings and leadership within and outside the ATVB council. AHA scientific sessions is promoting such initiatives by hosting WLC luncheons which I am excited to attend this afternoon.

Despite women pursuing careers in science are all too aware they remain underrepresentation in the field of science due to persisting gender inequality often which severely limits them from reaching their goals. AHA sessions provide great hopes to resolve this global concern by recognizing the challenges that women face in science, encouraging leadership programs and providing a platform that advances women’s scientific careers at all stages. I am proud of being part of such community and looking forward to exploring more aspects of AHA during my stay in Anaheim.  

Keerat Kaur Headshot

Keerat Kaur is a postdoctoral fellow at Icahn school of Medicine at Mount Sinai in department of cardiology, NY. Her research focuses on reprogramming non-cardiacmyocytes to cardiomyocytes using modified mRNA approach.